Asthma management: A new phenotype-based approach using presence of eosinophilia and allergy.

Asthma is a heterogeneous disease. The Czech Pneumology and Allergology Societies commissioned 10 experts to review the literature and create joint national guidelines for managing asthma, reflecting this heterogeneity. The aim was to develop an easy-to-use diagnostic strategy as a rational approach to the widening opportunities for the use of phenotype-targeted therapy. The guidelines were presented on websites for public comments by members of both the societies. The reviewers' comments contributed to creating the final version of the guidelines. The key hallmark of the diagnostic approach is the pragmatic concept, which assesses the presence of allergy and eosinophilia in each asthmatic patient. The guidelines define three clinically relevant asthma phenotypes: eosinophilic allergic asthma, eosinophilic nonallergic asthma and noneosinophilic nonallergic asthma. The resulting multifunctional classification describing the severity, level of control and phenotype is the starting point for a comprehensive treatment strategy. The level of control is constantly confronted with the intensity of the common stepwise pharmacotherapy, and the concurrently included phenotyping is essential for phenotype-specific therapy. The concept of the asthma approach with assessing the presence of eosinophilia and allergy provides a way for more precise diagnosis, which is a prerequisite for using widening options of personalized therapy.

[Chronic obstructive pulmonary disease in the light of new guidelines -  brief summary of phenotypically oriented guidelines for nonpulmonary physicians]. / Chronická obstrukcní plicní nemoc pohledem nových doporucení -  souhrn aktuálního fenotypove zamereného standardu Ceské pneumologické a ftizeologické spolecnosti pro internisty.

INTRODUCTION: COPD is a global health and social problem. Morbidity and mortality increases in the Czech Republic. There are currently several global statements and strategies. METHODS: The Czech Pneumological and Phthisiological Society (CPFS) at the end of 2011 mandated the Section of bronchial obstruction in drafting national guidelines concerning the stable COPD. Subsequently, this document was discussed during the National Consensus Conference (COPD forum) in November 2012 and presented at series of local workshops and national conferences. National guidelines has been subject to a review and eventually posted on the website for another round of comments. DIAGNOSIS: A modern approach to COPD is a view of the patient through the pulmonary function, symptoms, exacerbation rates and the presence of specific phenotypes. CPFS identified six clinically relevant phenotypes: frequent exacerbators, COPD and asthma overlap, COPD and bronchiectasis overlap, emphysematic phenotype, bronchitic phenotype and phenotype of pulmonary cachexia. TREATMENT: TREATMENT recommendations can be divided into four elementary steps: the first step is the Elimination of all risks factors. The second one is the Standard therapy including in particular inhaled bronchodilators, pulmonary rehabilitation, and treatment of severe comorbidities. The third step is the Targeted therapy centered on clinical phenotypes of COPD. The final fourth step is the treatment of respiratory insufficiency and palliative care of the terminal COPD. CONCLUSION: The optimal treatment of COPD requires a personalized approach to the patient.

Impairment of nasal mucociliary clearance in former smokers with stable chronic obstructive pulmonary disease relates to the presence of a chronic bronchitis phenotype.

BACKGROUND: Associations between nasal and bronchial impairment have been repeatedly described in chronic obstructive pulmonary disease (COPD), whereas nasal mucociliary clearance (MCC) in COPD patients is not yet fully understood. We studied nasal MCC parameters in COPD patients and compared them with healthy adults (HA) and with cystic fibrosis (CF) patients with compromised MCC. METHODOLOGY: An observational study of 98 COPD ex-smokers and subjects from control groups evaluated for nasal MCC time (NMCCt) and by digital video microscopy of nasal mucosa recording ciliary beat frequency (CBF) and ciliary beat pattern. RESULTS: The NMCCt was decreased in HA compared to those with COPD and decreased in those with COPD compared to those with CF. CBF in COPD was lower compared to HA. The index of ciliary dyskinesia in COPD patients differed from HA. We detected higher NMCCt and lower nasal CBF in patients with chronic bronchitis phenotype (CB) compared to non-CB patients. CONCLUSIONS: We confirmed the presence of impaired nasal MCC in COPD ex-smokers. These impairments were apparent predominantly in the CB phenotype.

Failure of noninvasive prediction of pulmonary hypertension in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary hypertension (PH) in patients with advanced idiopathic pulmonary fibrosis (IPF) is a complication connected with unfavorable prognosis. Great efforts have been made in attempting to establish a reliable non-invasive method which would enable detection of this complication. In this context a formula using pulmonary function parameters was published with outstanding results. METHODS: We tested the formula in 27 IPF patients who underwent a lung function examination, cardiac ultrasonography and catheterisation on the same day. RESULTS: Pulmonary hypertension was detected by catheterisation in 17 patients (63%). In our group, contrary to the published data, the aforementioned formula was neither useful for detecting patients with a high probability of PH nor as a means of calculating the mean pulmonary artery pressure in individual patients (p = 0.502 and p = 0.833, respectively). Ultrasound examination reached borderline correlation with the values measured by catheterisation when we compare patients with relevant results (r = 0.531, p = 0.051). However, the examination gave no usable results in 13 patients (48%). CONCLUSION: Our data suggests that no reliable, noninvasive method is currently available for detecting and confirming PH in IPF patients. We did not confirm the usefulness of the published formula. Further carefully organised studies will be necessary to verify or refute it.

[Relationship between quality of life and BODE index of stable ex-smokers with chronic obstructive pulmonary disease]. / Vztah mezi kvalitou zivota a BODE indexem u bývalých kuráku ve stabilní fázi chronické obstrukcní plicní nemoci.

BACKGROUND AND AIM: This study was carried out to assess relationship between quality of life (QoL) and disease severity expressed by multifactorial prognostic index (BODE) in ex-smokers suffering from chronic obstructive pulmonary disease (COPD), minimally 8 weeks free of exacerbation. MATERIALS AND METHODS: The evaluation was performed in 98 randomly recruited COPD patients enrolled into a cross-sectional, observational CILIARY study at the Department of Pneumology, Charles University, Faculty of Medicine in Hradec Králové. In them, quality of life evaluation using the SGRQ questionnaire and the BODE index calculation was performed. We statistically compared interrelationship between BODE and COPD stages, SGRQ and COPD stages and interrelation of BODE and SGRQ. RESULTS: We found significant differences in QoL of COPD patients and QoL in group of healthy volunteers (p <0.001). Lower QoL and higher BODE score were associated with a higher stages of COPD (p < 0.001), with the exception non-significant difference in QoL (SGRQ score) and BODE index between stages I and II. Our study found positive correlation between the all SGRQ scores and multidimensional prognostic BODE index (r = 0.431-0.704). The strongest correlation (r = 0.704) was evident in activity domain of SGRQ. CONCLUSION: Our results proved close correlation ofquality of life (SGRQ) and multidimensional prognostic score (BODE) in stable COPD exsmokers' population. Both these scoring systems are useful tools for the assessment of clinical course and stratification of severity of COPD. However at present both scales are minimally used in the Czech Republic.

[Examination of function and structure of respiratory cilia of adult patients suffering from chronic obstructive pulmonary disease (COPD)--comparison of nasal and bronchial mucosa (pilot of CILIARY STUDY)]. / Porovnání struktury a funkce nazální a bronchiální sliznice u nemocných s CHOPN (pilotní projekt ciliární studie).

INTRODUCTION: Borderline between upper and lower respiratory tract pathology is probably artificial (bronchial asthma). Also inflammation of bronchial mucosa during chronic obstructive pulmonary disease (COPD) is likely combined with inflammatory involvement of nasal mucosa. Ciliary edge of respiratory epithelium is very important part of mucosa layer. AIM: To investigate and compare nasal and bronchial ciliary beat frequency (CBF), degree of nasal and bronchial ciliary dyskinesia, presence of ciliary akinesia and incidence of spinocellular metaplasia in the both mucosa localities among of stable COPD patients (pts). METHOD: Nasal and bronchial mucosa were obtained in the course of bronchoscopy examination of COPD pts in general intravenous anesthesia. Native samples of mucosa tissue were assessed by digital high-speed video microscopy (1,000x magnification). Paired t-test was used to evaluate differences in average frequencies. Significance level was alpha = 0.05. Mode was used to describe "index of dyskinesia", as a measure of association was used K coefficient. MATERIAL: Seventeen COPD pts (6 weeks free of exacerbation) at the age 47-80 (average 64.2 years +/- 9.7) were examined (13 male), average FEV1 61% predic. value (21-81, +/- 15). All patients were active smokers (average 42 pack years +/- 22.8) and all suffered from bronchitic (daily sputum production) phenotype of COPD. RESULTS: We did not find any difference in average ciliary beat frequencies between nose (6.0 Hz +/- 1.3) and bronchus (5.9 +/- 1.3) locality (p = 0.427). We find weak association between nose and bronchus in "ciliary akinesia" (kappa = 0.282) but medium association in "metaplasia" (kappa = 0.485), in index of dyskinesia (kappa = 0.733). CONCLUSION: We did not find in our data any difference in nasal and bronchial ciliary beat frequencies and we found medium association between nasal and bronchial spinocellular metaplasia and index of ciliary dyskinesia. Possible generalization of these results would require further investigation and analysis.

[Twenty years of care for cystic fibrosis adults in Czech Republic]. / Dvacet let péce o dospelé nemocné s cystickou fibrózou v Ceske republice.

INTRODUCTION: Most of cystic fibrosis (CF) patients survive now into adulthood and they are transferred to pulmonologist care. AIMS: An overview of progress in care for CF adults in Czech Republic and evaluation of relationship of pulmonary function, nutritional status and airway colonization. METHODS: All adult CF patients followed in pulmonary departments from December 1987 to December 2007 were included into study. Data about survival status, pulmonary function, nutritional status, airway colonization and other pulmonary and extrapulmonary manifestations of CF were collected from patients' records. RESULTS: Total of 206 patients (96 females) were followed. Pancreatic insufficiency was present in 175 (85.0%), liver disease in 61 (29.6%) and insulin treatment in 58 (28.2%) patients. Bone disease was found in 70 (46.7%) from 150 examined patients. Sixty-two patients (23 females) died at mean age 25.4 +/- 5.5 years (median 24.3 years). Worse survival was recorded in patients with Burkholderia cepacia complex (BCC) airway colonization (24.4 +/- 4.0 vs 28.5 +/- 7.0 years, p = 0.012). One hundred forty-four living patients were followed to date of the 31st December 2007 with mean age 27.5 +/- 6.5 years (median 26.5 years), FEV1 64.4 +/- 28.5% pred. and BMI 20.9 +/- 3.1 kg/m2. Worse pulmonary function was present in patients with BCC colonization (FEV1 58.8 +/- 21.9 vs 67.8 +/- 27.3% pred., p = 0.041) and in malnourished patients (FEv1 49.5 +/- 18.5 vs 69.7 +/- 25.9% pred., p < 0.0001). BCC colonization was found in 54 (37.5%), Pseudomonas aeruginosa (PA) colonization in 92 (63.9%) and colonization without BCC or PA in 40 (27.8%) patients, respectively. Malnutrition (BMI < 19.0 kg/m2) was recorded in 38 (26.4%) patients. CONCLUSION: This study confirms growing number of CF adults in Czech Republic, close relationship of pulmonary function and nutritional status and also unfavourable influence of BCC colonization.

[Diagnosis of sleep apnea syndromes at the Medical School Hospital in Hradec Kralove]. / Diagnostika syndromu spánkové apnoe ve Fakultní nemocnici v Hradci Králové.

The authors present a short review of complex diagnostic procedure of sleep apnea syndrome in Hradec Králové Faculty Hospital.

The effect of triiodothyronine on changes of membrane fluidity in regenerating rat liver.

The increase of the membrane fluidity during the early phase of liver regeneration after partial hepatectomy was described in literature in plasma membrane and in microsomes. We found similar changes also in isolated mitochondria and in crude total membrane fraction of the liver homogenate. The administration of triiodothyronine to rats before partial hepatectomy diminished the increase of the membrane fluidity in the regenerating liver by 50%. Triiodothyronine effect is explained by hormonal modification of lipid metabolism in the regenerating liver.

The dream space and countertransference.

The author describes some similarities in the psychoanalytic literature between the conceptualisation of the dream space and that of the analyst's function as a container of the patient's projections. He also notes the correspondence between the creative use of a dream and the use of an analytic session to further understanding. Detailed clinical material is then presented from the analysis of two male patients, both of whom were unable to complete a dream about a particular emotional dilemma. The way in which they created severe disturbance in the countertransference at the same time is reported. The analyst's struggle to work through this difficulty and the beneficial consequences of this for the patient are described. It is argued that this demonstrates the way in which patients may project into the analyst dilemmas that they are unable to dream about in order that the analyst's functioning may transform the dilemmas into ones that can be thought and dreamt about. It is further argued that some patients have a developmental need to engage the analyst in this way.

[Anti-proteinuria effects of nonsteroidal anti-inflammatory drugs in patients with nephrotic syndrome: an illusion or a read improvement?]. / Antiproteinuricni efekat nesteroidnih antiinflamacionih lekova u bolesnika s nefrotskim sindromom: privid ili stvarno poboljsanje?

In order to examine the antiproteinuric effect of non-steroidal antiinflammatory drugs in patients with nephrotic syndrome, we performed a parallel determination of the daily proteinuria, strength of glomerular filtration and of the effective renal plasmatic flow in basal conditions and after a 7 day ibuprofen therapy at a daily dose of 1200mg (3 x 400mg) in a group of 12 patients with idiopathic glomerulonephritis. In all patients ibuprofen therapy induced a significant decrease of the existing proteinuria, but this decrease was accompanied by the decrease of clearance rate of 99mTc-DTPA and 131J-hipuran clearance, that is by decrease of strength of glomerular filtration (averagely 24.29%) and effective renal plasmatic flow (averagely 18.74%). It can be concluded that the decrease of proteinuria in patients with nephrotic syndrome after ibuprofen therapy (as well as other non-steroidal antiinflammatory drugs) is primarily the result of worsening of hemodynamic conditions in the kidney, that it is caused by the reduction of the renal blood flow and by the strength of glomerular filtration in conditions of cycloxygenetic activity inhibition in the kidney.

Effects of nonsteroidal antiinflammatory drugs on renal plasma flow and glomerular filtration rate in patients with glomerulonephritis.

We investigated the effects of NSAIDs (Ibuprofen) on renal plasma flow (RPF) and glomerular filtration rate (GFR) in patients with glomerulonephritis. The study included 98 patients (53 men and 45 women) with idiopathic glomerulonephritis. All of the patients received Ibuprofen 1200 mg (3x400) during 7 days. Before and after the treatment with Ibuprofen ERPF (clearance of 131I-Hippuran) and GFR (clearance of 99mTc-DTPA) were determined. In our patients administration of Ibuprofen was associated with a significant reduction in renal plasma flow and glomerular filtration rate. In patients with reduced renal function the decrease in RPF and GFR after Ibuprofen was significantly greater than in patients with normal renal function.

[Radionuclide functional tests in transplanted kidneys]. / Radionuklidno funkcijsko ispitivanje transplantiranog bubrega.

Results of 140 combined first-pass and dynamic functional renal studies were clinically evaluated in 50 patients with a transplanted kidney. The renal handling of three different nephroaffine radionuclides, namely the glomerular agent (99m Tc-DTPA), the predominantly tubular agent (99m TcMAG3) and combined glomerulo-tubular agent (99m Tc-PAHIDA) was also analysed in various dysfunctions of renal transplants. It has been concluded, that the clinically most useful information at all levels of the overall renal function has been given by 99m TcMAG3. However, the behaviour of glomerular and tubular agents in postischaemic acute tubular lesion was found to be discordant which in turn could be valuable differential-diagnostic information, and out of this reason their successive application is essential. The combined firstpass and dynamic functional renal studies have been judged as a helpful diagnostic tool in the follow-up of patients who have undergone kidney transplantation, provided that its results are interpreted in the light of clinical and other relevant findings.

[Evaluation of temporary work disability]. / Poznámky k posudzovaniu docasnej pracovnej neschopnosti.

The author discusses assessment of temporary work incapacity with special emphasis on responsible differentiation of biological and non-biological work incapacity. He emphasizes the importance of elimination of non-biological work incapacity. He deals with the problem of assessment of "serious cases" and advocates training of the character of people form early childhood to prevent abuse of leave granted for looking after a sick child or getting medical certificates to exempt children from physical training classes.

[The importance of beta-2 microglobulin determination in the urine in the detection of tubular proteinuria]. / Znacaj odredivanja beta-2 mikroglobulina u urinu u detekciji proteinurije tubulskog tipa.

In 38 patients with the positive finding of protein in the urine the determination of beta-2 microglobulin concentration was made in addition to the simultaneous determination of albumin, IgC and transfer in the urine and the calculation of differential protein clearance values for the identification of tubular proteinuria. Only 4 (10.53%) patients had proteinuria of tubular type, 16 patients had proteinuria of glomerular type, while proteinuria of the mixed glomerulo-tubular type was found in 18 (47.37%) patients. The safe separation of tubular proteinuria from that of glomerular type was made possible by the determination of beta-2 microglobulin concentration in the urine in the framework of detailed investigation.