Exercise Tolerance in Patients With Idiopathic Pulmonary Fibrosis, Effect of Supplemental Oxy-Gen.

Exercise tolerance in patients with idiopathic pulmonary fibrosis IPF is mainly limited by mechanical constrain of ventilation and high physiologic dead space. Oxygen enriched gas inhalation seems to increase ventilatory efficiency by reduction of dead space to tidal volume ratio (VD/VT) which probably mirrors improved pulmonary capillary flow and leads to longer physical tolerance at lower level of minute ventilation. The effect is noticeable at FIO2 that can be delivered in rehabilitation purposes or daily living activities.

[Radiotherapy of Lung Tumours in Idiopathic Pulmonary Fibrosis]. / Radioterapie nádoru s plicní lokalizací u idiopatické plicní fibrózy.

BACKGROUND: This article is a joint statement of the Czech Pneumological and Physiological Society and the Czech Society for Radiation Oncology, Biology and Physics, and reviews current opinions on radiotherapy in patients with idiopathic pulmonary fibrosis (IPF). In general, radiotherapy of lung tumours is associated with risk of radiation pneumonitis (RP); moreover, IPF may be complicated by acute exacerbations (AE-IPF). Both complications may immediately threaten patients lives. MATERIAL AND METHODS: Assessment of individual radiotherapy modalities has shown that conventional radiotherapy is not appropriate, especially in large tumours. Up to 30% of patients are at risk of developing AE-IPF. As a result, as many as 83% of patients die within 3 months of initiation of lung cancer treatment. Fatal RP is most commonly observed within 2 months of radiotherapy. In IPF accompanied by early-stage non-small cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) may be considered. NSCLC should be treated with chemotherapy. Several cases report severe exacerbations of subclinical IPF after SBRT even with minimal signs of previous interstitial involvement. Grade 2 RP has been reported in up to 50% of cases with any level of interstitial change detected by lung CT prior to radiotherapy. In palliative radiotherapy, external radiation may be considered as an exception if the main bronchi are involved. Similarly, brachytherapy may be indicated for certain cases of bronchial stenosis. RESULTS: The presence of any level of interstitial change suggests a risk for fatal RP and AE-IPF. This is also supported by the fact that, at the present time, there are no dose limitations for radiation therapy of lung cancer in IPF, irrespective of whether conventional fractionated radiotherapy or SBRT is used. Moreover, there are no reliable predictive factors for lung involvement. In some studies, RP was more frequently associated with high CRP and LDH levels, PS 2 and interstitial changes of 10% or more. Treatment depends on the severity of the involvement. In more severe forms, corticosteroids, antibiotics and oxygen therapy should be administered. Ventilation support is often needed. CONCLUSION: Radiotherapy for patients with IPF and lung cancer or other chest tumours requires an individual approach depending on the local findings, the patients lung function and general condition, and the prognosis of the primary disease. Decision-making should take into consideration potential benefits and risks, and be carried out by a multidisciplinary team comprising a pulmonologist and clinical and radiation oncologists. Treatment should always be thoroughly discussed with the patient signing an informed consent form.Key words: idiopathic pulmonary fibrosis - chest radiotherapy - indications - radiation pneumonitis - acute exacerbation of idiopathic pulmonary fibrosis - treatment This work was supported by grant AZV 16-32-318 A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 5. 2017Accepted: 18. 5. 2017.

Significance of specific IgG against sensitizing antigens in extrinsic allergic alveolitis: serological methods in EAA.

The aim of our study is to find differences in IgG in sera of potentially exposed and nonexposed individuals and to detect differences in concentrations of specific serum IgG among subjects with and without EAA. Seventy-two patients being followed for suspected interstitial lung disease were included. Specific IgG in sera were established by ImmunoCAP. Serum concentrations of Aspergillus fumigatus, Candida albicans IgG and mixture of moulds IgG were higher in subjects with exposure to relevant inhalation antigens (p<0.05). Patients exposed to parrot and mammal hair mixture had higher serum concentration of specific IgG (p<0.05). Subjects without exposure to mites had lower serum IgG to Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermatophagoides microceras and Glycophagus domesticus (p<0.05). Higher concentration of serum specific IgG may show previous exposure to this antigen. Even though mite specific IgG are not commonly tested in EAA patients, we suggest their immunomodulatory activity may influence susceptibility to other inhalation antigens.

Cytokine gene polymorphisms in sarcoidosis.

BACKGROUND: Sarcoidosis is a disease characterized by granuloma formation in many organs, but mostly in lung and lymph nodes. The immunopathogenic background of the disease is probably based on disregulation of immune response to different antigens. The imbalance of immune reactivity might be influenced by genetic background. In our study, we have investigated cytokine genetic polymorphisms in sarcoidosis group and compared the results with that of a group of healthy volunteers. METHODS: Thirty one sarcoidosis patients were enrolled to our study. Basic demographic data were collected. Polymorphisms in the promoter regions of the IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-alpha, IFN-gamma and in the translated regions of the TGF-beta, IL-1 beta, IL-2, IL-4 and IL-4RA genes were characterized. RESULTS: For IL-10, the (-819) and (-592) CC homozygosity was statistically more frequent in the sarcoidosis group compared to healthy controls. According to the haplotypes, the majority of sarcoidosis patients had IL-10 (-1082)(-819)(-592) ACC haplotype 2 compared to controls with ATA in most of the cases. CONCLUSIONS: The results of our study support the hypothesis of a genetically encoded immune regulation imbalance in sarcoidosis. The high-producer IL-10 (-819) and (-592) CC genotypes and intermediate- producer IL-10 (-1082) (-819) (-592) ACC haplotype 2 present in the majority of our sarcoidosis patients could support the role of genetically encoded disregulation of cell- mediated immune response to an unknown antigen.

Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases.

Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and sarcoidosis belong to interstitial lung diseases (ILD) where an imbalance of regulatory, profibrotic and antifibrotic cytokines is hypothesized. The relationship of bronchoalveolar lavage (BAL) fluid (BALF) cytokines, BALF cell profile and ILD course is supposed. The aim of our study was to correlate BALF cytokine and chemokine levels with BALF cellular characteristics and lung function parameters in different ILD. Twenty-two sarcoidosis, seven IPF and 11 HP patients underwent lung function tests and BAL. The BALF differential cell counts and superficial cell markers were characterized, and MCP-1, MIP-1alpha, MIP-1beta, RANTES, epithelial neutrophil-activating protein (ENA)-78, FGF, G-CSF, GM-CSF, IFN-gamma, interleukin (IL)-1alpha, IL-1RA, IL-1beta, -2beta, -4beta, -5beta, -6beta, -8beta, -10beta, -17beta, tumour necrosis factor (TNF)-alpha, thromobopoietin (Tpo) and vascular endothelial growth factor (VEGF) values measured. The BALF VEGF values were highest in sarcoidosis (P = 0.0526). IL-1RA values were higher in IPF and HP compared with sarcoidosis (P = 0.0334). IL-8/ENA-78 ratio positively correlated with BALF neutrophil counts in IPF (r = 0.89, P = 0.04). Vital capacity and TL(CO) values positively correlated with VEGF and negatively with IL-8 BALF levels in all ILDs but the correlations were most significant in sarcoidosis group. We suppose that VEGF plays a role in ILDs' early phases and has rather angiogenic than profibrotic effect. On the contrary, IL-8 is probably upregulated in advanced ILDs with prominent fibrosis and marked lung functions decline. We state that BALF VEGF, IL-8 and ENA-78 levels and IL-8/ENA-78 ratio could become useful markers of ILDs' phase, activity and prognosis. They might also be helpful in treatment modality choice.

Extrinsic allergic alveolitis: comparative study of the bronchoalveolar lavage profiles and radiological presentation.

INTRODUCTION: Extrinsic allergic alveolitis (EAA) is an immunologically mediated interstitial lung disease. The abnormalities in the bronchoalveolar lavage (BAL) fluid cell counts are almost always seen in patients with EAA according to the stage of the disease. The aim of this retrospective study was to find out how the BAL lymphocyte count, percentage of lymphocytes expressing HLA-DR, CD4/CD8 T cell ratio in BAL fluid, and the concentration of immunoglobulin G in serum correspond to the inflammatory activity of the disease. METHODS: The study included 14 patients with EAA. BAL fluid samples were obtained and processed for cytological and cytometric analysis. Immunoglobulin G serum concentrations were measured. High resolution computed tomography (HRCT) scoring system modified by Gay was used for establishing the alveolar and interstitial score in each patient. CONCLUSIONS: It was found that subjects with normal value of CD4/CD8 ratio in BAL fluid had higher interstitial HRCT score. Clinical presentation, continuous exposure to the causative antigens, and BAL lymphocyte count positively correlated with the alveolar HRCT score. It is proposed that the increased BAL lymphocyte count could be the predictor of the inflammatory activity of the disease, especially in people with lasting exposure to the offending antigen.