Are obesity and asthma in school-age children still strongly related to breastfeeding in infancy? - A real-life study.

OBJECTIVE: Although breastfeeding has been suggested as a candidate for the prevention of obesity and allergies, recent studies have reported mixed results. The aim of the study was (1) to assess breastfeeding length in obese children or children with allergic diseases compared to healthy children; (2) to evaluate the impact of the duration of breastfeeding on the incidence of obesity, allergy rhinitis and asthma. PATIENTS AND METHODS: 408 children were evaluated (mean age 11.9±3.7 years; M/F 220/188) and divided into three groups (Obesity, n=103; Allergy, n=163; and Healthy, n=142). Breastfeeding history was collected during an interview. Physical examination, anthropometry, allergy (skin prick test with aeroallergens; Allergopharma) and a spirometry (Jaeger) assessment were performed in each participant. RESULTS: Most of the children (75%) were breastfed with a mean duration of 7.5 months (range 0-36; SD=7.9 months). The time of breastfeeding was longer in the healthy compared to the obese and allergic groups (p=0.003) and was correlated with BMI centile in all groups of subjects (R Spearman = -0.2, p<0.05). There was a higher number of subjects with hypersensitivity to the allergen of house dust mites and animals in the non-breastfed compared to the breastfed children (p<0.003, p<0.000, respectively). Non-breastfed children compared to the breastfed presented more often asthma (chi2=3.6 df=1 p=0.05), but not allergic rhinitis (chi2=9.0 df=1 p=0.002). Non-breastfed asthmatics, compared to the breastfed asthmatics, presented a significantly higher severity of asthma (OR=0.43; p=0.008). In multivariate regression models, a short breastfeeding time was associated with a higher risk of both obesity and asthma. CONCLUSIONS: School-age children with obesity and asthma were breastfed less often and for a shorter duration than their healthy peers. Longer breastfeeding may result in a reduced number of children with obesity, asthma, and allergy to house dust mites, but further investigation is needed on a larger population of school-age children.

Recommendations for Lung Ultrasound in Internal Medicine

A growing amount of evidence prompts us to update the first version of recommendations for lung ultrasound in internal medicine (POLLUS-IM) that was published in 2018. The recommendations were established in several stages, consisting of: literature review, assessment of literature data quality (with the application of QUADAS, QUADAS-2 and GRADE criteria) and expert evaluation carried out consistently with the modified Delphi method (three rounds of on-line discussions, followed by a secret ballot by the panel of experts after each completed discussion). Publications to be analyzed were selected from the following databases: Pubmed, Medline, OVID, and Embase. New reports published as of October 2019 were added to the existing POLLUS-IM database used for the original publication of 2018. Altogether, 528 publications were systematically reviewed, including 253 new reports published between September 2017 and October 2019. The new recommendations concern the following conditions and issues: pneumonia, heart failure, monitoring dialyzed patients' hydration status, assessment of pleural effusion, pulmonary embolism and diaphragm function assessment. POLLUS-IM 2020 recommendations were established primarily for clinicians who utilize lung ultrasound in their everyday clinical work.

Prognostic value of microRNA expression in operable non-small cell lung cancer patients.

BACKGROUND: About 50% of non-small cell lung cancer (NSCLC) patients develop distant metastases following pulmonary resection. Currently, there are no reliable factors allowing for individual selection of high-risk patients for adjuvant systemic therapies. METHODS: We assessed by quantitative reverse transcription PCR microRNA (miRNA) expression in 273 stage I-IIIA NSCLC samples. Expression of 677 miRNAs was evaluated in fresh-frozen tumour samples in the training cohort of 50 squamous cell carcinoma (SCC) patients who underwent curative surgery. Of those, 20 patients developed distant metastases, and 30 were free of recurrence for >4 years. In the second step, miRNAs with highest predictive value for distant relapse were re-evaluated in formalin-fixed paraffin-embedded material in an independent group of 134 stage I-IIIA SCC patients. Additionally, the same miRNAs were investigated in 89 lung adenocarcinoma (AC) patients and in normal lung parenchyma (NLP). RESULTS: In the training cohort of SCC, six miRNAs were differently expressed in the non-recurrent vs recurrent groups and correlated with distant recurrence-free survival, however none reached the level of significance after correction for multiple testing. Of these six miRNAs, miR-662, -192 and -192* were confirmed as prognostic in the independent SCC cohort. Expression of miR-128, -10b, -502-3p and -192 differed between SCC and AC, and miR-128 and -192 - between NLP and NSCLC. CONCLUSIONS: We identified three new miRNAs predictive of distant relapse in operable SCC. Future miRNA studies should account for differences between NSCLC subtypes.

The influence of obesity on inflammation and clinical symptoms in asthma.

Obesity and asthma are both important public health issues. Increasing number of studies suggest the association between obesity and asthma which may be causal or accidental. The studies on animal models show innate enhancement of airway hyper-responsiveness which suggest that chronic airway hyper-responsiveness may be related to chronic low-grade systemic inflammation occurring in obesity. These results are confirmed by studies on asthmatic patients which show that levels of inflammation markers were higher in obese asthma patients and are related to the parameters of obesity. However, adipokines secreted by adipose tissue have also been involved in the regulation of inflammation and allergic responses, and suggested to affect the risk of asthma, especially in obese female patients. The studies on the association between adiposity and atopy have conflicting results and the issue needs to be investigated in the future. Obesity also decreases lung volume and increases airway resistance inducing symptoms that could mimic asthma. Clinical studies suggest that asthma in obese subjects may differ from the classical phenotype of the disease. Obese patients referred for asthma exacerbation present a reduced response to standard asthma medications. The review indicates that mechanical and inflammatory effects of obesity may explain the influence on asthma. Further studies on the association between adiposity and atopy on airway inflammation may confirm the active role of fat tissue, not only simple mechanical impairment of the thorax movement. Longitudinal studies are needed to understand the association between asthma, and obesity, which may open new therapeutic options for asthma treatment in obese patients.

Molecular profiles of non-small cell lung cancers in cigarette smoking and never-smoking patients.

PURPOSE: Molecular features of non-small cell lung cancer (NSCLC) in never-smokers are not well recognized. We assessed the expression of genes potentially related to lung cancer etiology in smoking vs. never-smoking NSCLC patients. METHODS: We assayed frozen tumor samples from surgically resected 31 never-smoking and 54 clinically pair-matched smoking NSCLC patients, and from corresponding normal lung tissue from 27 and 43 patients, respectively. Expression of 21 genes, including cell membrane kinases, sex hormone receptors, transcription factors, growth factors and others was assessed by reverse transcription - quantitative PCR. RESULTS: Expression of 5 genes was significantly higher in tumors of non-smokers vs. smokers: CSF1R (p<0.0001), RRAD (p<0.0001), PR (p=0.0004), TGFBR2 (p=0.0027) and EPHB6 (p=0.0033). Expression of AKR1B10 (p<0.0001), CDKN2A (p<0.0001), CHRNA6 (p<0.0001), SOX9 (p<0.0001), survivin (p<0.0001) and ER2 (p=0.002) was significantly higher in tumors compared to normal lung tissue. Expression of AR (p<0.0001), EPHB6 (p<0.0001), PR (p<0.0001), TGFBR2 (p<0.0001), TGFBR3 (p<0.0001), ER1 (p=0.0006) and DLG1 (p=0.0016) was significantly lower in tumors than in normal lung tissue. Expression of IGF2 was higher in tumors than in healthy lung tissue in never-smokers (p=0.003), and expression of AHR (p<0.0001), CSF1R (p<0.0001) and RRAD (p<0.0001) was lower in tumors than in healthy lung tissue in smokers. CONCLUSION: Expression of several genes in NSCLC is strongly related to smoking history. Lower expression of PR and higher expression of ER2 in tumors suggests a possibility of hormonal therapeutic intervention in selected NSCLC patients. Distinct molecular features of NSCLC in never-smokers, e.g. CHRNA6 upregulation, may prompt new treatment strategies.

Gene expression profile, pathways, and transcriptional system regulation in indolent systemic mastocytosis.

BACKGROUND: Mastocytosis is an uncommon disease resulting from proliferation of abnormal mast cells infiltrating skin, bone marrow, liver, and other tissues. The aim of this study was to find differences in gene expression in peripheral blood cells of patients with indolent systemic mastocytosis compared to healthy controls. The second aim was to define a specific gene expression profile in patients with mastocytosis. METHODS: Twenty-two patients with indolent systemic mastocytosis and 43 healthy controls were studied. Whole genome gene expression analysis was performed on RNA samples isolated from the peripheral blood. For amplification and labelling of the RNA, the Illumina TotalPrep 96 RNA Amplification Kit was used. Human HT-12_V3_expression arrays were processed. Data analysis was performed using GeneSpring, Genecodis, and Transcriptional System Regulators. RESULTS: Comparison of gene expression between patients and controls revealed a significant difference (P < 0.05 corrected for multiple testing) and the fold change difference >2 in gene expression in 2303 of the 48.794 analysed transcripts. Functional annotation indicated that the main pathways in which the differently expressed genes were involved are ubiquitin-mediated proteolysis, MAPK signalling pathway, pathways in cancer, and Jak-STAT signalling. The expression distributions for both groups did not overlap at all, indicating that many genes are highly differentially expressed in both groups. CONCLUSION: We were able to find abnormalities in gene expression in peripheral blood cells of patients with indolent systemic mastocytosis and to construct a gene expression profile which may be useful in clinical practice to predict the presence of mastocytosis and in further research of novel drugs.

Role of quantitative chest perfusion computed tomography in detecting diabetic pulmonary microangiopathy.

AIMS: Aim of the study was to determine the role of perfusion chest computed tomography (pCT) in evaluation of pulmonary diabetic angiopathy. METHODS: 18 never-smoking patients (10 diabetic patients and 8 healthy controls) underwent chest high resolution CT (HRCT) and then pCT scanning. In both groups, blood tests, biochemical analysis, fibrinogen, HbA(1c), spirometry, diffusion capacity for carbon monoxide (DLCO) and body pletysmography were performed.Following parameters of pulmonary perfusion have been analysed: blood volume (BV), blood flow (BF), mean transit time (MTT), time to peak (TTP) and permeability surface (PS). RESULTS: there were no statistically significant differences between groups in terms of age, sex, BMI, forced expiratory volume in one second (FEV(1)), DLCO. Chest HRCT revealed no pathologies. Significantly higher values of chest pCT for BF (p=0.05), BV (p=0.05) and PS (p=0.01) have been found in diabetics in comparison to controls. No differences were found in MTT. CONCLUSIONS: significant increase of perfusion parameters in diabetes seems to confirm pulmonary microangiopathy. The results indicate that further studies on application of pCT in diabetic patients may be beneficial for better understanding of lung microangiopathy, its diagnosing and monitoring.

Gene expression analysis predicts insect venom anaphylaxis in indolent systemic mastocytosis.

BACKGROUND: Anaphylaxis to insect venom (Hymenoptera) is most severe in patients with mastocytosis and may even lead to death. However, not all patients with mastocytosis suffer from anaphylaxis. The aim of the study was to analyze differences in gene expression between patients with indolent systemic mastocytosis (ISM) and a history of insect venom anaphylaxis (IVA) compared to those patients without a history of anaphylaxis, and to determine the predictive use of gene expression profiling. METHODS: Whole-genome gene expression analysis was performed in peripheral blood cells. RESULTS: Twenty-two adults with ISM were included: 12 with a history of IVA and 10 without a history of anaphylaxis of any kind. Significant differences in single gene expression corrected for multiple testing were found for 104 transcripts (P < 0.05). Gene ontology analysis revealed that the differentially expressed genes were involved in pathways responsible for the development of cancer and focal and cell adhesion suggesting that the expression of genes related to the differentiation state of cells is higher in patients with a history of anaphylaxis. Based on the gene expression profiles, a naïve Bayes prediction model was built identifying patients with IVA. CONCLUSIONS: In ISM, gene expression profiles are different between patients with a history of IVA and those without. These findings might reflect a more pronounced mast cells dysfunction in patients without a history of anaphylaxis. Gene expression profiling might be a useful tool to predict the risk of anaphylaxis on insect venom in patients with ISM. Prospective studies are needed to substantiate any conclusions.

Mastocytosis and insect venom allergy: diagnosis, safety and efficacy of venom immunotherapy.

The most important causative factor for anaphylaxis in mastocytosis are insect stings. The purpose of this review is to analyse the available data concerning prevalence, diagnosis, safety and effectiveness of venom immunotherapy (VIT) in mastocytosis patients. If data were unclear, authors were contacted personally for further information. Quality of evidence (A: high, B: moderate, C: low and D: very low) and strength of recommendation (strong 1 and weak 2) concerning VIT in mastocytosis patients are assessed according to the Grading of Recommendations Assessment, Development and Evaluation and are marked in square brackets. Results of VIT were described in 117 patients to date. The mean rate of side-effects during treatment in studies published so far is 23.9% (7.6% requiring adrenaline) with an overall protection rate of 72%. Based on the review we conclude that (1) mastocytosis patients have a high risk of severe sting reactions in particular to yellow jacket, (2) VIT could be suggested [2] in mastocytosis, (3) probably should be done life long [2], (4) VIT in mastocytosis is accompanied by a higher frequency of side-effects, so (5) special precautions should be taken into account notably during the built up phase of the therapy [2], (6) VIT is able to reduce systemic reactions, but to a lesser extent compared to the general insect venom allergic population [2], so (7) patients should be warned that the efficacy of VIT might be less than optimal and they should continue carrying two adrenaline auto injectors [2].

Interleukin-13 promoter gene polymorphism -1112C/T is associated with the systemic form of mastocytosis.

BACKGROUND: Mastocytosis is a heterogenous disease involving mast cells (MC) and their progenitors. Cutaneous and systemic variants of the disease have been reported. In contrast to cutaneous mastocytosis (CM), patients with systemic mastocytosis (SM) are at risk to develop disease progression or a nonMC-lineage haematopoietic neoplasm. Little is known, however, about factors predisposing for the development of SM. One factor may be cytokine regulation of MC progenitors. METHODS: We examined the role of the interleukin-13 (IL-13) promoter gene polymorphism -1112C/T, known to be associated with increased transcription, in mastocytosis using allele-specific polymerase chain reaction method. Serum tryptase and IL-13 levels were determined by immunoassay, and expression of the IL-13 receptor in neoplastic MC by reverse transcription-polymerase chain reaction and flow cytometry. RESULTS: The frequency of the -1112T allele of the IL-13 promoter was significantly higher in patients with SM compared with CM (P < 0.008) and in mastocytosis patients compared with healthy controls (P < 0.0001). Correspondingly, the polymorphism was found to correlate with an elevated serum tryptase level (P = 0.004) and with adult-onset of the disease (P < 0.0015), both of which are almost invariably associated with SM. Serum IL-13 levels were also higher in SM patients compared with CM (P = 0.011), and higher in CT- than in CC carriers (P < 0.05). Finally, we were able to show that neoplastic human MC display IL-13 receptors and grow better in IL-13-containing medium. CONCLUSIONS: The -1112C/T IL-13 gene polymorphism and the resulting 'hypertranscription' may predispose for the development of SM.

Prognostic value of S-100 immunostaining in tumour cells of non-small cell lung cancer.

S-100 protein expression is present in various malignant tissues, yet its prognostic relevance is debatable. The aim was to assess in non-small cell lung cancer (NSCLC) patients' prognostic value of S-100 protein considered alone or in relation with other variables. Tumour samples taken from 86 NSCLC patients during resection were assayed for S-100 protein expression with the use of polyclonal DAKO ZO311 antibody. S-100 expression was found in 32 cases (37%). Positive staining was not correlated with clinical characteristics including age, sex, pathology type of tumour, stage and cigarette smoking. There was a tendency for simultaneous expression of S-100 and P53 protein (p=0.06). A median survival rate for the entire group was 2.3 years (95% CI, 0.9-3.6 years). The median and 5-year survival of patients with positive staining for S-100 protein was 1.5 years and 25%, respectively, compared with 3.0 years and 35%, respectively, in the S-100 negative group (p=0.17). In the final model of a multivariate analysis, S-100 protein expression in tumour cells was associated with significantly decreased survival (p=0.005). S-100 protein expression in tumour cells seems to be an independent predictor of poor prognosis in NSCLC patients.

Drug intolerance in patients with idiopathic environmental intolerance syndrome.

The increasing rate of the idiopathic environmental intolerance (IEI) has been observed for the last decade. The aim of this report was to analyse the allergic component of the disease in particular relation to drug intolerance. Six patients with diagnosed IEI showed a positive skin test reaction to several commonly used antibiotics, nonsteroidal anti-inflammatory drugs, myorelaxants, verapamil, etc. In three cases, the thorough diagnosis of sensitivity to anaesthetic agents enabled to perform necessary surgical treatment, in others - facilitated the proper treatment of headaches and hypertension. Symptoms related to allergy contributed to the deterioration of IEI. Thus, a consultation of IEI patients by an allergologist seems to be of a substantial importance.

Clinical significance of apoptotic index in non-small cell lung cancer: correlation with p53, mdm2, pRb and p21WAF1/CIP1 protein expression.

PURPOSE: The aim of this study was to assess the prognostic relevance of apoptotic index (AI), considered alone or together with expression of several proteins controlling G1 check point (p53, mdm2, pRb and p21WAF1/CIP1) in non-small cell lung cancer (NSCLC) patients. METHODS: Study group included 50 NSCLC patients who underwent curative pulmonary resection. Apoptosis was detected with the use of TUNEL technique and AI was defined as the number of apoptotic cells per 1,000 tumor cells. The expression of p53, mdm2, pRb and p21WAF1/CIP1 was assessed immunohistochemically. RESULTS: The mean and median AI calculated for all 50 patients was 14 and 9, respectively. Patients with lower (<14) and higher (> or =14) AI constituted 35 (70%) and 15 (30%) of cases, respectively. AI was not correlated with patient clinical characteristics, and expression of p53, pRb and p21WAF1/CIP1 . However, lower AI was correlated with over-expression of mdm2 protein (P=0.04). Median survival for patients with lower and higher AI was 43 months and 22 months, respectively, and 5-year survival probability-60 and 25%, respectively (P=0.03). In multivariate analysis, the only variable associated with shortened survival was AI (P=0.03, HR=2.9, 95% CI 1.95-3.86). CONCLUSIONS: These results suggest that AI correlates with mdm2 protein expression and influences survival in NSCLC.

Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer.

Prognostic value of p53 and PCNA expression in non-small cell lung cancer (NSCLC) remains controversial. In this study we determined the relevance of these abnormalities in terms of overall survival and disease-free survival in 95 NSCLC patients who underwent curative pulmonary resection. Expression of p53 was found in 44 samples (45%), expression of PCNA-in 79 samples (83%), and expression of both markers-in 35 samples (36%). There was no relationship between expression of either protein and major clinicopathological characteristics. Median survival for patients with and without p53 expression was 36 and 33 months, respectively and 5-year survival probability-29 and 37%, respectively (P=0.73). Median survival for patients with and without PCNA expression was 36 and 27 months, respectively and 5-year survival probability-35 and 25%, respectively (P=0.60). There was no significant difference in overall survival between particular groups of patients with tumors carrying four possible p53/PCNA phenotypes. In multivariate analysis including patient age, sex, tumor stage, tumor type and differentiation, p53 and PCNA expression, the only variable important for survival was stage of disease. These results suggest the lack of prognostic relevance of p53 and PCNA expression in surgically treated NSCLC patients.

Types and localisation of p53 gene mutations: a report on 332 non-small cell lung cancer patients.

Mutations of p53 suppressor gene are among the most common molecular abnormalities in human malignancies. We demonstrated earlier significant differences in mutational profiles between NSCLC patients from Poland and Spain. These differences were most probably related to ethnic and/or geographical factors. In the present study we analyzed the types and location of p53 gene mutations in a large group of 332 operated NSCLC patients from two institutions in Northern Poland. Within the last decades this region has been characterized by the highest incidence of lung cancer in Poland. We used both frozen and paraffin-embedded tumor samples and the screened region included exons from 5 to 8. A total of 96 samples (29%) were positive for p53 gene mutation. The proportion of mutations in particular exons was as follows: exon 5-33%, exon 6-22%, exon 7-16%, and exon 8-29%. Three 'hot spots' were located in codons 176,245 and 248. Evolutionary conserved domains were much more frequently affected than the regions outside domains. The majority of mutations (73%) were missense type, followed by null and silent mutations (21 and 6%, respectively). In all six silent mutations substituted was the third base in codon. There were no major differences in the types and locations of mutations between patients from the two institutions. This homogeneity, together with our earlier findings, may confirm the impact of ethnic and geographical factors on the mutational profile of p53 gene in NSCLC.

[Molecular basis of carcinogenesis in lung cancer induced by cigarette smoking]. / Molekularne podstawy indukcji raka pluca pod wplywem palenia tytoniu.

An association between cigarette smoking and lung cancer carcinogenesis is reviewed. It is highly possible, that "individual susceptibility" for tumor development exists and is related to polymorphic variants of genes encoding for enzymes, which are employed in metabolism of xenobiotic substances. The gathering of highly reactive molecules due to modified metabolic processes results in DNA adducts forming and increased tendency for mutations. Group of genes, responsible for proliferation, cell cycle arrest, apoptosis and DNA damage repair are frequently altered.

Serum p53 antibodies in small cell lung cancer: the lack of prognostic relevance.

Prognostic relevance of serum p53 antibodies was assessed in 96 patients with microscopically proven small cell lung cancer (SCLC). The study group included 67 males and 29 females; mean age 58 years; range 35--86 years; 60 with limited disease (LD), and 36 with extensive disease (ED). The control group consisted of 41 patients with non-malignant diseases. The presence of p53 antibodies was assayed by the immunoenzymatic method (P53 ELISA kit, PharmaCell, France). Antibodies were present in 26 SCLC cases (27%); 15 (25%) in LD and 11 (31%) in ED. Antibodies were also found in one out of 41 control subjects (2%). There was no correlation between the level of antibodies and clinical characteristics of SCLC patients including age, gender and extent of disease. The median follow-up for the entire group was 30 months (range: 11--39 months). By the time of analysis, 78 patients (82%) had deceased. Median survival in SCLC patients with and without antibodies was 42 and 39 weeks, respectively (log rank, P=0.81). These results indicate the lack of clinical relevance of serum p53 antibodies in SCLC.

Expression of vascular endothelial growth factor (VEGF) and its receptor FLK-1 in non-small cell lung cancer (NSCLC)--a preliminary report.

The assessment of tumour angiogenesis in NSCLC is presently a subject of intensive research with potential clinical applications. In this study, the expression of VEGF and FLK-1 was examined by immunohistochemistry in 67 archival tumour samples obtained from NSCLC patients treated by radical resection. Distribution of age, sex, tumour stage and histology was typical for patient population in Poland. VEGF expression (more than 25% of positive cells) was noted in 65% of tumour cells. FLK-1 expression was observed in 91% of tumour cells. Neither the number of positive cells nor the staining intensity correlated with the clinical variables (all p values >0.05, chi-square test). No correlation was noted between the expression of VEGF and FLK-1 (p=0.35, chi-square test). In survival analysis, neither the number of positive cells nor the staining intensity of both molecules was of prognostic significance. The expression of VEGF and FLK-1 in NSCLC cells was confirmed in this study. The relation to clinical variables and survival will be further assessed in a larger group of patients.

The prevalence of cigarette smoking among school pupils staying at summer camps.

SETTING: The prevalence of cigarette smoking in Poland is one of the highest in Europe. OBJECTIVE: To compare the frequency of smoking among Polish pupils during a school year and the summer holidays. DESIGN: A questionnaire including personal and demographic data and information on smoking behaviour was distributed among 598 school pupils: 357 girls and 241 boys aged 8-19 years, with a mean age of 14.4. RESULTS: Among the entire group of school pupils, 18.6% were cigarette smokers. Half of the smokers smoked occasionally and the remainder smoked every day; of these, 9.9% smoked more than 10 cigarettes daily. The frequency of smoking among these teenagers increased with age. The average age of smoking initiation was 13 years for boys and 15 years for girls. The majority smoked more during the summer holidays than during the school year. The most frequently reported reasons for increasing cigarette smoking during the summer holidays were: feeling more free, having more money to spend, the influence of new friends, and smoking to pass the time when they felt bored. CONCLUSION: Young people in this study still started smoking early, most frequently between the ages of 13 and 15. High rates of daily smokers among teenagers were observed. In some groups of teenagers the summer holidays may be a time of increased cigarette smoking.