Lung cancer is the most common malignant neoplasm and constitutes the most common neoplastic cause of death globally. The results of therapies employing standard chemotherapy are unsatisfactory. Currently, efforts are being made to personalize the therapy; numerous clinical studies are being conducted around the world to assess the efficacy and safety of agents directed at molecular targets. One of these molecular targets is the c-MET proto-oncogene, whose primary ligand is hepatocyte growth factor (HGF). C-MET hyperactivity has been observed in numerous neoplasms, including non-small-cell lung carcinoma. Prolonged or continuous activity of the receptor leads to excessive cell proliferation and is related to the development or progression of neoplastic disease. C-MET inhibitors can be classified into three groups: small-molecule tyrosine kinase inhibitors of the c-MET receptor (crizotinib, tivantinib, cabozantinib, foretinib), as well as monoclonal antibodies against c-MET (onartuzumab) and against the HGF ligand (ficlatuzumab, rilotumumab). The efficacy and safety of these agents is assessed both in monotherapy and in combination with other molecularly targeted agents. Furthermore, the toxicity profile of c-MET inhibitors is completely different from that of standard chemotherapy. The best understood c-MET inhibitor used in the treatment of non-small-cell lung carcinoma patients is crizotinib. It is registered for patients with the presence of ALK gene rearrangements after the failure of the first line of treatment based on platinum derivatives. The purpose of this present paper is to present clinical studies that assessed the efficacy and safety of c-MET inhibitors for the treatment of non-small-cell lung carcinoma, as well as current indications for the use of these molecules.

Background Cystic fibrosis (CF) is one of the most common autosomal recessive diseases. Factors contributing to disease exacerbations and survival rate of CF patients are type of mutation in the CFTR gene, poor nutritional status, lung failure, and infection development by Pseudomonas aeruginosa. The study aimed to evaluate the relationship between the severity of mutation, nutritional status, lung function, and Pseudomonas aeruginosa prevalence and survival rate in adult patients with cystic fibrosis. Methods A study of 124 (68 ♀ and 56 ♂) adults with CF aged 18–51 years were evaluated for (a) type of mutation in the CFTR gene, (b) nutritional status (BMI), (c) lung function (FEV1%), and (d) Pseudomonas aeruginosa prevalence. For statistical calculations, Kaplan-Meier analysis of survival, chi-squared test for multiple samples, and logistic regression were used. Results The type of mutation (χ2 = 12.73, df = 3, p = 0.005), FEV1% (χ2 = 15.20, df = 2, p = 0.0005), Pseudomonas aeruginosa prevalence (χ2 = 11.48, df = 3, p = 0.009), and BMI (χ2 = 31.08, df = 4, p < 0.000) significantly differentiated the probability of survival of patients with CF. The shortest life expectancy was observed in patients with a severe type of mutation on both alleles, FEV1% < 40, subjects in whom Pseudomonas culture was extensively drug-resistant or pandrug-resistant, and patients whose BMI was lower than 18.5 kg/m2. The period from 30 to 40 years of age was the most critical in CF adults’ lifespan. The risk of adults with CF death doubled with Pseudomonas aeruginosa prevalence (OR = 2.06, 95% CI 1.29; 2.28) and eightfold when the bacteria acquired antibiotic resistance (OR = 8.11, 95% CI 1.67; 38.15). Conclusions All factors included in the study were significantly related to the survival rate of patients with cystic fibrosis.

The impulse oscillometry (IOS) is recognized as a complementary method to spirometry in the diagnostics of obstructive pulmonary disorders. The IOS enables to measure total respiratory resistance (R5) and proximal respiratory resistance (R20), with the R5-R20 difference reflecting small airway resistance. This study seeks to evaluate the usefulness of R5-R20, maximal mid-expiratory flow (MMEF) and forced expiratory volume in 3 s/forced vital capacity ratio (FEV/FVC), in the assessment of small airway obstruction in chronic obstructive pulmonary disease (COPD). One hundred and six COPD patients and 43 control subjects, aged over 55, were investigated. Spirometry and IOS were used to assess pulmonary function. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were evaluated. The findings demonstrate significant reductions in FEV/FVC and MMEF, and an increase in R5-R20 difference in COPD patients; the changes that depended on the severity of airway obstruction. The sensitivity of R5-R20 in reflecting the MMEF was 84%, specificity 44.2%, PPV 72.4%, and NPV 61.3%. We conclude that the R5-R20 difference is superior to spirometry in the assessment of small bronchi obstruction. A high sensitivity of R5-R20 in reflecting the MMEF makes the IOS method particularly useful for detection of mild lung injury, while a high specificity of the spirometric FEV/FVC ratio makes it useful to exclude obstruction of small airways. Both methods are thus complimentary.

The purpose of the study was to evaluate the influence of nutrition and of the severity of mutation type on survival rate in cystic fibrosis (CF) patients. Data were longitudinally collected from 60 hospitalized adult CF patients, aged 18-50. The variables consisted of body mass index (BMI) ratio, Cole's BMI cut-off points, severity of mutation type, and survival rate of CF patients. We found that the mean BMI was strongly associated with the severity of mutation type and was significantly lower in patients with severe mutations of grade I and II. The mutation type significantly affected the patients' survival rate; survival was greater in patients with mild and undefined mutation types. The BMI and Cole's cut-off points also had a significant influence on survival rate. CF patients, who suffered from malnutrition and emaciation, had a shorter survival rate than those with proper nutritional status. In conclusion, the study findings confirmed a significant effect of nutritional status and of mutation type on survival rate of CF patients.

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