Pregnancy in women with cystic fibrosis: 14 case reports and literature review / Cystás fibrosisban szenvedo nok várandóssága: 14 eset ismertetése és irodalmi áttekintés

Összefoglaló. A cystás fibrosisban szenvedo betegek várható élettartama jelentosen megnott az utóbbi évtizedben, egyre több beteg képes saját gyermeket vállalni. Célunk a cystás fibrosisban szenvedo várandós nok perinatalis és anyai történéseinek felmérése saját eseteink és az irodalmi adatok alapján. 14, cystás fibrosisban szenvedo no 16 várandósságáról számolunk be. Rögzítettük a várandósok életkorát, testtömegét, testmagasságát, testtömegindexét, légzésfunkciós értékeit a graviditás kezdetén és végén. Az anyai átlagéletkor szüléskor 21,6 (18-25) év volt. Az anyák graviditásának kezdetén a testmagasság átlaga 162 (150-175) cm, a testtömeg átlaga 57,6 (42-72) kg, a testtömegindex átlaga 21,4 (19,1-23,2) kg/m2 volt. A graviditás végén a testtömeg átlaga 62 (39-76) kg, a testtömegindex átlaga 23,6 (21,3-24,1) kg/m2 volt. A graviditás alatti súlygyarapodás átlaga 8 (1,5-21,5) kg volt. A légzésfunkciós értékek a graviditás kezdetén 2 betegnél voltak beszukültek. A graviditás alatt még 2 beteg légzésfunkciós értékei csökkentek. A sikeres graviditások száma 13 volt. 1 anya kétszer szült. A koraszülések száma 1 volt. A várandósság átlagosan a 38. (34-40.) gestatiós hét után 7 esetben császármetszéssel, 6 esetben hüvelyi szüléssel fejezodött be. A vetélések száma 3 volt. Az Apgar-pontszám minden esetben normális volt. 13 gyermek közül 11-nél a verejtékteszt nem volt emelkedett. 2 gyermeknél magas verejtékértékek voltak, egyikük c.1521_1523delCTT-heterozigóta, a másiknál génmutációt nem tudtunk igazolni. A cystás fibrosisban szenvedo nok általában jól tolerálják a várandósságot az esetek többségében. A kórosan beszukült tüdofunkcióval, alacsony tápláltsági állapottal és cukorbetegséggel rendelkezo nok nagyobb valószínuséggel számíthatnak káros következményekre. Az újszülöttek prognózisa általában jó, de számítani kell a koraszülés és a kis súllyal születés gyakoribb elofordulására. Ideális esetben a várandósságot elozetes tanácsadás útján kell megtervezni, és speciális cystás fibrosis csoportnak kell a várandósok ellátását figyelemmel kísérni, ideértve a cystás fibrosis kezelésében jártas szülészeket is. Kisszámú saját adatunk retrospektív elemzése megerosíti az irodalmi adatok tanúságait. Orv Hetil. 2021; 162(28): 1129-1136. Summary. The life expectancy of patients with cystic fibrosis has increased significantly in the last decade, with more and more patients being able to have their own children. The aim of our study was to assess the perinatal and maternal outcome of pregnant women with cystic fibrosis based on our own cases and literature data. We report 16 pregnancies in 14 women with cystic fibrosis. We recorded the age, body weight, height, body mass index, and respiratory function values of pregnant women at the beginning and end of pregnancy. The mean maternal age at childbirth was 21.6 (18-25) years. At the beginning of maternal pregnancy, the mean height was 162 (150-175) cm, the mean body weight was 57.6 (42-72) kg, and the mean body mass index was 21.4 (19.1-23.2) kg/m2. At the end of pregnancy, the mean body weight was 62 (39-76) kg and the mean body mass index was 23.6 (21.3-24.1) kg/m2. The weight gain under pregnancy was mean 8 (1.5-21.5) kg. The respiratory function values at the onset of pregnancy were narrowed in 2 patients. During pregnancy, the respiratory function values of 2 more patients decreased. The number of successful gestations was 13. A mother gave birth twice. The number of premature births was one. The pregnancy after the mean 38. (34-40.) gestational week was completed in 7 cases by cesarean section and in 6 cases by vaginal delivery. The number of miscarriages was 3. The Apgar score was normal in all cases. In 11 of 13 children, the sweat test was not elevated. 2 children had high sweat values, one of them is heterozygous with c.1521_1523delCTT, the other could not prove a gene mutation. Women with cystic fibrosis generally tolerate pregnancy well, in most cases. Women with poor lung function, low nutritional status, and diabetes are more likely to expect adverse consequences. The outcome of the newborns is good in general, but a common occurrence of premature birth and low birth weight is to be expected. Ideally, pregnancy should be planned through prior counseling and the care of pregnant women should be monitored by a specialized cystic fibrosis team, including obstetricians experienced in the treatment of cystic fibrosis. A retrospective analysis of our own small-number data confirms the evidence from the literature data. Orv Hetil. 2021; 162(28): 1129-1136.

First 3 Years of the Hungarian Lung Transplantation Program.

In this article we summarize the results of the first 3 years after launching the Hungarian Lung Transplantation Program. PATIENTS AND METHODS: The first lung transplant in Hungary was carried out on December 12, 2015, with the collaboration of the National Institute of Oncology and the Semmelweis University. Up to December 31, 2018, a total of 62 lung transplants were performed. Data were analyzed retrospectively. Patients were listed for lung transplant after the indication was established by the National Lung Transplantation Committee. Donor lungs were procured from brain-dead donors only. RESULTS: Within this period our team was involved in 87 lung procurements, 61 of which resulted in bilateral lung transplant and 1 in single-sided transplant. The operative approach was unilateral thoracotomy (n = 1), bilateral thoracotomy (n = 1), or clamshell incision (n = 60) with venoarterial extracorporeal membrane oxygenation support. The underlying disease of the recipients was obstructive lung disease (n = 30), lung fibrosis (n = 11), cystic fibrosis (n = 18), primary pulmonary hypertension (n = 2), histiocytosis-X syndrome (n = 1), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and retransplant because of bronchiolitis obliterans syndrome (n = 1). The youngest patient was 13 years of age, while the oldest was 65 years. Three patients died in the early postoperative phase. One-year survival was 80%. DISCUSSION: The number of cases rises steadily in the Hungarian Lung Transplantation Program, which is exceptional compared with the start of other centrums. The incidence of complications and mortality is comparable with those of other experienced centers around the world. Our future goal is to broaden our waiting list, thus increasing the number of lung transplants carried out.

[The start of the Hungarian lung transplantation program and the first results]. / A magyar tüdotranszplantációs program indulása és elso eredményei.

The first lung transplantation in Hungary was performed on 12th of December, 2015. It was a joint effort of the National Institute of Oncology and the Semmelweis University. Hereby we summarise the results and experiences from the first three years. Until August, 2018, 55 lung transplantations were performed in Hungary. This was a retrospective analysis. All patients were listed according to the recommendation of the Lung Transplantation Committee. All implanted lungs have been procured from brain dead donors. Postoperative treatment and rehabilitation of the patients were continued at the Semmelweis University. Between 12. 12. 2015 and 31. 07. 2018, our team performed 76 organ retrievals: out of 45 Hungarian offers, 23 came from Eurotransplant countries and 8 outside of the Eurotransplant region. From these donations, 54 double and 1 single side transplantations were successfully performed. The surgical approach was single side thoracotomy (n = 1), bilateral thoracotomy (n = 1) and in the majority of the cases clamshell incision (n = 53). For the intraoperative veno-arterial extracorporeal membrane oxygenation support was used. The extracorporeal membrane oxygenation support had to be prolonged in 3 patients into the early postoperative period, two other recipients were bridged to transplant with extracorporeal membrane oxygenation. In the same time period, one combined lung-kidney transplantation was also performed. The distribution of recipients according to the underlying disease was: chronic obstructive pulmonary disease (n = 28); idiopathic pulmonary fibrosis (n = 8); cystic fibrosis (n = 12); primary pulmonary hypertension (n = 2); hystiocytosis-X (n = 1); bronchiectasis (n = 2); lymphangioleiomyomatosis (n = 1); and re-transplantation following bronchiolitis obliterans syndrome (n = 1), respectively. The mean age of recipients was 47.5 ± 15.18 years. The youngest recipient was 13 years old. We unfortunately lost 12 patients on our waiting list. The mean intensive care unit stay was 24.6 ± 18.18 days. Two patients were lost in the early postoperative phase. Tracheostomy was necessary in 13 cases due to the need of prolonged ventilation. 1-year survival of the recipients was 82.96% (until 31. 07. 2018). When looking at the first three years of the program, the case numbers elevated quickly throughout the years which is rather unique when compared to other centres in their starting period. Perioperative mortality and morbidity is comparable with high-volume lung transplantation centres. In the future we would like to increase the number of patients on the waiting list, thus increasing the total number of transplantations performed, and we are also planning to implement the use of the ex vivo lung perfusion system (EVLP) in our program. Orv Hetil. 2018; 159(46): 1859-1868.

Exhaled breath condensate pH in patients with cystic fibrosis.

OBJECTIVE AND DESIGN: Exhaled breath condensate (EBC) pH has been proposed as a useful, non-invasive marker of airway inflammation in pulmonary diseases. In this study we tested whether cystic fibrosis (CF) is associated with acidification of EBC, when pH is assessed by the CO(2) gas standardization method. METHODS: EBC was collected using two different devices (EcoScreen and R-Tube) in 46 stable CF patients during routine clinical visits and in 28 healthy controls. RESULTS: Mean EBC pH in CF patients and in healthy controls was similar (EcoScreen: CF patients: 6.38 ± 0.03 versus controls: 6.39 ± 0.03, p = 0.699; R-tube: CF patients: 5.94 ± 0.04 versus controls: 6.02 ± 0.03, p = 0.159). Inflammatory cell counts in spontaneously expectorated sputum obtained in a subset of patients (n = 20) showed no correlation with pH values. EBC samples collected with the R-tube were more acidic than those collected with the EcoScreen device (p < 0.001). CONCLUSIONS: Our data suggest that EBC pH does not discriminate between healthy controls and those with CF disease indicating that the clinical applicability of EBC pH measurements for assessing airway inflammation in CF is limited.

Exhaled breath condensate pH in lung transplant recipients with bronchiolitis obliterans syndrome.

BACKGROUND: Assessment of exhaled breath condensate (EBC) pH is a promising method for investigating airway pathology. However, inaccurate measurement techniques may bias pH readings. In this longitudinal study, we tested whether development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients is associated with acidification of EBC. METHODS: EBC was collected in 15 patients with BOS and 16 stable BOS-free patients during routine clinical visits. From nine BOS patients, samples were collected before and after the onset of BOS, as well. Twenty healthy nontransplant subjects served as controls. EBC pH was measured by the carbon dioxide gas standardization method. RESULTS: EBC pH in patients with and without BOS and controls was similar (BOS group: 6.40±0.04, BOS-free group: 6.45±0.03; controls: 6.39±0.02; P>0.05). In patients who developed BOS during the follow-up, EBC pH before and after the onset of BOS was comparable (pre-BOS: 6.41±0.04 vs. post-BOS: 6.41±0.04; P>0.05). Coefficient of variation for repeated pH measurements in controls and subjects with and without BOS was 2.3%±0.3%, 2.0%±0.3%, and 1.7%±0.2%, respectively (P>0.05). Similarly, the limits of agreement for between-visit variability determined by the Bland-Altman test were comparable among the study groups. CONCLUSIONS: These data suggest that assessment of EBC pH is of limited value for the diagnosis of BOS.

Assessment of exhaled breath condensate pH in exacerbations of asthma and chronic obstructive pulmonary disease: A longitudinal study.

RATIONALE: Exhaled breath condensate pH has been proposed as a noninvasive marker of airway inflammation. However, due to standardization difficulties in pH measurement techniques, different pH readings were obtained in previous studies. OBJECTIVES: In this longitudinal study we assessed condensate pH in patients with an exacerbation of asthma or chronic obstructive airway disease using the very precise carbon dioxide standardization method that negates the effect of this gas on condensate acidity. METHODS: Condensate pH, fractional exhaled nitric oxide, lung function, and blood gases were measured in 20 nonsmoking patients with asthma and 21 smoking and 17 ex-smoking patients with chronic obstructive airway disease first at hospital admission due to an acute exacerbation of the disease and again at discharge after treatment. Condensate pH was also assessed in 18 smoking and 18 nonsmoking healthy control subjects. MEASUREMENTS AND MAIN RESULTS: In patients with asthma, condensate pH was significantly decreased at the time of exacerbation compared with nonsmoking control subjects and increased with treatment. In patients with chronic obstructive airway disease, condensate pH remained unchanged during exacerbation, both in smokers and ex-smokers. Nevertheless, condensates collected from smokers were more acidic than those of ex-smokers. A similar difference was observed between smoker and nonsmoker healthy control subjects. No correlations were found between condensate pH and fractional exhaled nitric oxide or lung function variables measured either at admission or discharge. CONCLUSIONS: Our data suggest that exacerbation of asthma, but not chronic obstructive airway disease, is associated with acidification of breath condensate.

Relationship between exhaled nitric oxide and treatment response in COPD patients with exacerbations.

BACKGROUND AND OBJECTIVE: Fractional exhaled nitric oxide (FENO) has been implicated as a pulmonary biomarker in various respiratory diseases, including COPD. In this longitudinal study, the benefit of measuring FENO in a routine clinical setting was assessed in COPD patients hospitalized with an exacerbation of the disease. METHODS: FENO, lung function and blood gases were measured in 58 COPD patients at hospital admission due to an exacerbation, and at discharge following treatment with corticosteroids and bronchodilators. RESULTS: FENO levels were significantly decreased at discharge, compared with those at admission (geometric mean 25.3 ppb (95% CI: 21.2-30.1) vs 19.7 ppb (95% CI: 17.2-22.6); P = 0.002). There was a significant positive correlation between FENO concentrations at admission and the increase in FEV(1) after treatment (r = 0.441, P < 0.001), and a significant inverse correlation between FENO values at admission and the mean length of hospital stay (r = -0.297, P = 0.016). Using receiver operating characteristic curve analysis, the optimum cut point for FENO as a predictor for significant increase in FEV(1) was 26.8 ppb (sensitivity: 74%, specificity: 75%). There were no correlations between FENO levels and absolute values for lung function variables at admission or discharge. CONCLUSIONS: These data suggest that FENO levels determined at hospital admission may predict the overall response to treatment in COPD patients with acute exacerbations.

Analysis of cytokine pattern in exhaled breath condensate of patients with squamous cell lung carcinoma.

Exhaled breath condensate (EBC) analysis is a promising method for investigating airway pathology. In this study we compared the cytokine pattern of EBC of patients suffering from squamous cell lung carcinoma with that of healthy smokers. Breath condensates collected from 8 smoking lung cancer patients before receiving any anticancer treatment and 8 smokers without any clinical or radiological evidence of pulmonary tumors were used for antibody microarray analysis testing 120 cytokines simultaneously. Ninety-eight cytokines on the array gave a detectable signal in both groups. Cytokine levels were similar across the samples, and none of the cytokines exhibited a significant increase or decrease in cancer patients as compared to healthy subjects with similar smoking status, lung function, and airway inflammation. The results of this pilot study suggest that patients with squamous cell lung carcinoma cannot be distinguished from smokers with no pulmonary tumors based on EBC cytokine signals only.

Analysis of cytokine pattern in exhaled breath condensate of lung transplant recipients with bronchiolitis obliterans syndrome.

INTRODUCTION: Exhaled breath condensate (EBC) analysis is a promising method for investigating airway pathology. In this pilot study we tested the cytokine pattern of EBC of lung transplant patients with and without clinical evidence of bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: Breath condensates collected from eight BOS patients and eight stable BOS-free lung transplant recipients in three consecutive visits were pooled in order to increase protein concentration and were then used for antibody microarray analysis detecting 120 cytokines simultaneously. RESULTS: Nine cytokines exhibited more than twofold increase and four exhibited more than twofold decrease in BOS patients as compared to stable subjects. CONCLUSION: We conclude that inflammatory cytokines are present in EBC of lung transplant recipients, however the potential benefit of detecting the EBC proteome warrants further studies.

Remission of left Tawara-branch block under treatment for systemic sarcoidosis.

Diagnosis and treatment of cardiac sarcoidosis is a challenging task. The presented case illustrates the importance of systemic ECG in the management of patients with pulmonary sarcoidosis and the utility of cardiac MRI in the diagnostic procedure of cardiac involvement of the disease. It is one of the first reports emphasising the recovery of a bundle branch block under treatment for sarcoidosis. The presented case supports the application of steroid-methotrexate combination in the treatment of cardiac sarcoidosis.

[The first 12 years of Hungarian lung transplantation]. / A tüdôtranszplantáció magyar történetének elsô 12 éve.

12 years have passed since the first Hungarian patient went through lung transplantation. A small but dedicated group of clinicians work to make lung transplantation an easily accessible, accepted therapy for Hungarian patients. Transplantation is recommended for patients suffering from end stage vascular or parenchymal diseases of the lung after conservative therapies are proven unsuccessful. Lung transplantation as a surgical intervention is currently not available in Hungary. In the past 12 years 64 Hungarian patients were transplanted at the Department of Cardiothoracic Surgery, Medical University of Vienna, in Austria by the Vienna Lung Transplant Group led by Prof. Walter Klepetko. Our patients went through lung transplantation for the following indications: cystic fibrosis (22), idiopathic lung fibrosis (18), primer pulmonary hypertonia (8), lymphangioleimyomatosis (5), emphysema (4) and other (7). The 64 patients altogether went through 68 transplantation procedures. In 4 cases re-transplantation was necessary. The surgery techniques employed were as follows: bilateral lung transplantation (33), bilateral lobar transplantation (18), single lung transplantation (13), heart-lung transplantation (2) and split-lung transplantation (2). Bilateral living-donor lung lobar transplantation was performed in one case. The mean age of patients at the time of surgery was 33.3 years (between age 14 and 58). 48 of the 64 patients are still alive.

Differential cytokine pattern in the exhaled breath of patients with lung cancer.

Tumour cells may alter the protein pattern of biological samples resulting in specific differences that may aid diagnosis and treatment. In this pilot study we tested the cytokine pattern of exhaled breath condensate of patients with lung cancer. Breath condensates collected from 50 smoking patients with lung cancer and 25 smokers without clinical or radiological sign of a pulmonary tumour but having co-morbidities with similar severity as those with lung cancer were pooled for antibody microarray analysis testing 120 cytokines in parallel. Every cytokine on the array gave a signal in both groups. Nine cytokines including eotaxin, FGFs, IL-10 and MIP-3 were present with more than two-fold difference between the two groups. Large number of cytokines is present in the exhaled breath. Further analysis of specific differences associated with lung cancer may have clinical importance.

[Pulmonary infections after lung transplantation]. / Tüdotranszplantált betegek pulmonalis infekciói.

Lung transplantation has become an accepted therapeutic modality for end-stage diseases of the lungs and the pulmonary circulation. In the past two decades more than 20,000 lung transplantations were performed all over the world. Due to improvements in immunosuppressive regimens the mortality rate of severe acute rejections has decreased up to 2% in the first post-transplant year. By contrast, infections became the most common cause of morbidity and mortality after lung transplantation. It was reported that 21.2 and 40% of annual deaths are due to infections in the first 30 days and one year, respectively. In the first month 35-70% of transplant recipients develop bacterial pneumonia caused often by Gram-negative organisms especially by Pseudomonas species. All patients should receive prophylactic antibiotics after the operation, which are to be modified according to the resistance patterns of pathogens isolated from the donor lungs. In the early post-operative period, the frequency of invasive fungal (Aspergillus and Candida) and cytomegalovirus (CMV) infections appears to be less then 10% due to prophylactic amphotericin inhalation and systemic valganciclovir administration for 100 days. After withdrawing these drugs, these infections became more common. In the late post-transplant period, the development of bronchiolitis obliterans syndrome (BOS) may predispose to infections. BOS may be manifested in approximately 50% of patients 5 years post-transplant. Routinely or urgently performed screening tests (laboratory and radiological investigations, lung function tests, sputum culture, bronchoscopy) and specific treatments are of central importance in the management of infections. In this review we discuss the clinical manifestation, the diagnosis and the treatment possibilities of the most common pulmonary infections in lung transplant recipients.

Variability of exhaled breath condensate pH in lung transplant recipients.

BACKGROUND: Measurement of pH in exhaled breath condensate (EBC) may represent a novel method for investigating airway pathology. OBJECTIVES: The aim of this longitudinal study was to assess the variability of EBC pH in stable lung transplant recipients (LTR). METHODS: During routine clinical visits 74 EBC pH measurements were performed in 17 LTR. EBC pH was also measured in 19 healthy volunteers on four separate occasions. EBC pH was determined at standard CO2 partial pressure by a blood gas analyzer. RESULTS: Mean EBC pH in clinically stable LTR and in controls was similar (6.38 +/- 0.09 vs. 6.44 +/- 0.16; p = nonsignificant). Coefficient of variation for pH in LTR and controls was 2.1 and 2.3%, respectively. The limits of agreement for between-visit variability determined by the Bland-Altman test in LTR and healthy volunteers were also comparable (-0.29 and 0.46 vs. -0.53 and 0.44). CONCLUSIONS: Our data suggest that the variability of EBC pH in stable LTR is relatively small, and it is similar to that in healthy nontransplant subjects.

[New diagnostic method in pulmonary carcinoid]. / Uj diagnosztikus módszer pulmonalis carcinoidban.

In clinical oncology tumor markers could be helpful in diagnostics, and may play a complementary role beside the imaging systems in the follow up of patients with malignant disease. Chromogranin A can be considered as a marker in neuroendocrine malignancies such as pulmonary carcinoids. Based on recommendations adopted from the literature, the authors measured chromogranin A levels in sera of patients with carcinoid tumors of different stages. Although the patient number is low, our data suggest that in cases where carcinoid metastasis can be detected, chromogranin A levels are elevated.

A formulation of aerosolized tobramycin (Bramitob) in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection: a double-blind, placebo-controlled, multicenter study.

BACKGROUND AND AIM: Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) causes progressive deterioration in lung function. The purpose of this trial was to assess the efficacy and tolerability of a tobramycin highly concentrated solution for inhalation (TSI) [300mg/4mL; Bramitob when added to other antipseudomonal therapies in CF patients with chronic P. aeruginosa infection. METHODS: In a multinational, double-blind, multicenter study, CF patients with chronic P. aeruginosa infection were randomized to receive nebulized tobramycin or placebo over a 24-week study period in which 4-week treatment periods ('on' cycles) were followed by 4-week periods without treatment ('off' cycles). Forced expiratory volume in 1 second (FEV(1)) percentage of predicted normal was used as the primary efficacy outcome parameter. Forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF(25)(-)(75%)), P. aeruginosa susceptibility, minimum concentration required to inhibit 90% of strains (MIC(90)), rates of P. aeruginosa-negative culture, P. aeruginosa persistence and superinfection, need for hospitalization and parenteral antipseudomonal antibiotics, loss of school/working days due to the disease, and nutritional status (bodyweight and body mass index) were considered as secondary efficacy outcome parameters. Adverse events reporting, audiometry, and renal function were monitored to evaluate the tolerability and safety of TSI. RESULTS: A total of 247 patients were randomized in the study. At endpoint time assessment (week 20), FEV(1) was significantly increased in the tobramycin group and the adjusted mean difference between groups (intention-to-treat population) was statistically significant (p < 0.001). At the same time, clinically relevant improvements in FVC and FEF(25-75%) were detected in the TSI group (p = 0.022 and p = 0.001, respectively). The microbiologic outcomes at the end of the last 'on' cycle period were significantly better in the TSI group than the placebo group (p = 0.024), although there was a concomitant trend toward an increase in the MIC of isolated P. aeruginosa strains. The percentage of patients hospitalized as well as the need for parenteral antipseudomonal antibiotics was significantly lower in the TSI group (p = 0.002 and p = 0.009, respectively). Patients treated with TSI had fewer lost school/working days due to the disease (p < 0.001). A favorable effect of tobramycin in terms of an increase in bodyweight and body mass index was also noted, when compared with placebo, at all time points (p < 0.01 and p < 0.001, respectively). No significant changes in serum creatinine and auditory function were detected. The proportion of patients with drug-related adverse events was 15% in both treatment groups. CONCLUSIONS: Long-term, intermittent administration of this aerosolized tobramycin formulation (300mg/4mL) in CF patients with P. aeruginosa chronic infection significantly improved pulmonary function and microbiologic outcome, decreased hospitalizations, increased nutritional status, and was well tolerated.

The 8.1 ancestral MHC haplotype is associated with delayed onset of colonization in cystic fibrosis.

Major cause of death in patients with cystic fibrosis (CF) is colonization with Staphylococcus aureus and Pseudomonas aeruginosa. The wide phenotypic variation in CF patients suggests that genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene modify the disease. The 8.1 ancestral haplotype (8.1AH) in main histocompatibility complex is associated with alterations of the immune response. To study the influence of carriage of 8.1AH on frequency and onset of colonization in CF patients, DNA samples of 72 CF patients (39 homozygous and 33 heterozygous for DeltaF508) were genotyped for member alleles of the 8.1AH: HLA-DQB1*0201, HLA-DRB1*0301, receptor for advanced glycation end products (AGER) -429C, HSP70-2 -1267G (HSP70-2G) and tumor necrosis factor-alpha (TNF-alpha) -308A (TNF2). Colonization was verified by regular clinical and bacteriological screening. Frequency of colonization was significantly (P = 0.012) lower in the 8.1AH carriers; age, gender and DeltaF508 genotype-adjusted odds ratio to be colonized of the carriers versus non-carriers was 0.112 (0.024-0.520). According to survival analysis, patients with 8.1AH had significantly (P < 0.0001) longer colonization-free period compared with non-carriers. Our novel observations demonstrate that the 8.1AH is associated with delayed onset of colonization in CF, presumably by influencing defense mechanisms against infections.

[New diagnostic methods of sarcoidosis in Hungary: labial biopsy and cardiac MRI]. / Uj lehetoségek a sarcoidosis diagnosztikájában magyarországon: ajakbiopszia és szív-MRI.

The two major challenges in the diagnostic procedure of sarcoidosis are the differential diagnosis and the determination of the extent of the disease. 1) The corner stone of differential diagnosis is the histological demonstration of non-caseating granulomas. Obtaining an appropriate sample for histological examination often requires invasive examinations. A minimal invasive sampling method, the labial biopsy, not yet practiced in Hungary is showed in the first part of this paper. 2) Cardiac involvement has great importance in the evaluation of the extent of the disease. MRI is the most accurate method available to date to demonstrate cardiac sarcoidosis. The first MRI proven cardiac sarcoidosis in the Hungarian medical literature is reported in the second part of the article.

[Bronchiolitis obliterans syndrome in lung transplant recipients]. / Bronchiolitis obliterans szindróma a tüdotranszplantáción átesett betegekben.

Bronchiolitis obliterans syndrome in lung transplant recipients. The leading cause of late graft loss after lung transplantation is bronchiolitis obliterans syndrome. The process is a manifestation of chronic rejection, and is characterized by an excessive fibroproliferation in the small airways, leading progressively to luminal obliteration and graft injury. Both alloantigen-dependent (acute rejection, histocompatibility) and alloantigen-independent (ischaemia-reperfusion injury, cytomegalovirus infection, gastroesophageal reflux disease) risk factors may contribute to the development of the disease. Early in the process, damage to the airway epithelium occurs, which then triggers a massive influx of alloreactive T-cells into the graft tissue. Activated T-cells release a wide range of cytokines and growth factors, which in turn are capable of stimulating cellular proliferation and matrix protein synthesis in fibroblasts as well as in airway smooth muscle cells. Clinically, a decline in lung functions together with nonspecific symptoms can usually be observed in these patients, while later in the disease course recurrent respiratory tract infections are more common. Up till now, no effective therapy is available for bronchiolitis obliterans syndrome, however, certain immunosuppressive regimens may slow down the progression of the disease.