Factors influencing quality of life and disease severity in Hungarian children and young adults with cystic fibrosis.

BACKGROUND: The aim of our study was to evaluate factors affecting cystic fibrosis (CF) patients' health-related quality of life (HRQoL) and to assess the level of agreement on HRQol between children and their parents. METHODS: Fifty-nine patients (mean age: 14.03 ± 4.81 years) from 5 Hungarian CF centres completed the survey. HRQoL was measured using The Cystic Fibrosis Questionnaire-Revised (CFQ-R). Parents were asked to fill out a questionnaire about their smoking habits, educational level and history of chronic illness. Disease severity was assessed using the physician-reported Shwachman-Kulczycki (SK) score system. Spirometry, Body Mass Index (BMI) percentile (pc), hospitalisation and Pseudomonas aeruginosa (PA) infection were examined as physiologic parameters of CF, and the impact of these factors on HRQoL was assessed. A multivariate regression analysis was performed to identify the most important factors affecting HRQoL. The level of significance was set to 0.05. RESULTS: Passive smoking and parental educational level and chronic diseases status did not have a significant impact on the patients' HRQoL (p > 0.05). Significantly lower SK scores and spirometry values were found in low BMI pc patients (p < 0.001), in hospitalised (p < 0.01) and in PA-infected patients (p < 0.01), than in the adequate-weight, non-hospitalised and PA culture-negative subgroup. Lower CFQ-R scores were detected in hospitalised patients than in non-hospitalised patients in their Physical functioning domain. PA-infected patients had HRQoL scores that were significantly worse in the Body image (p < 0.01) and Respiratory symptoms (p < 0.05) domains than the PA culture-negative patients. Patients with a low BMI pc (<25th BMI pc) had significantly lower scores in the Eating, Body image and Treatment burden domains, than the adequate-weight patients (>25th BMI pc) (p < 0.01). A strong child-parent agreement was found in the Physical functioning domain (r = 0.77, p < 0.01). CONCLUSIONS: Passive smoking, parental educational level and chronic diseases of parents do not affect the HRQoL of CF patients. In contrast, hospitalisation, PA infection and malnutrition have a significant and negative impact on patients' HRQoL and the clinical severity of the disease. Parents and children were consistent in their scoring of symptoms and behaviours that were observable.

[Quality of life in Hungarian patients with cystic fibrosis]. / Cystás fibrosisban szenvedo betegek életminoségének felmérése Magyarországon.

INTRODUCTION: Cystic fibrosis is a progressive multisystemic disease which affects the quality of life of patients. AIM: The aim of the study was to evaluate quality of life in Hungarian patients with cystic fibrosis. METHODS: Validated Hungarian translation of The Cystic Fibrosis Questionnaire - Revised was used to measure quality of life. Clinical severity was determined on the basis of Shwachman-Kulczycki score. Lung function was measured using spirometry. RESULTS: 59 patients were included from five centres in Hungary. The relationships between 8-13 year-old children self-report and parent proxy report was 0.77 (p<0.001) in physical functioning, 0.07 (p<0.001) in emotional functioning, 0.51 (p<0.001) in eating, 0.21 (p<0.001) in treatment burden, 0.54 (p<0.001) in body image, 0.49 (p<0.001) in respiratory symptoms and 0.40 (p<0.001) in digestive symptoms domains. CONCLUSIONS: In contrast to physical domains weak correlations were observed between answers obtained from children and their parents in psychosocial domains. The perception of both patients and their parents should be assessed when measuring quality of life in paediatric patients with cystic fibrosis.

Human enterovirus 109 (EV109) in acute paediatric respiratory disease in Hungary.

Human enterovirus 109 (EV109) is a recently identified recombinant enterovirus in family Picornaviridae from acute paediatric respiratory illness in Nicaragua. EV109 have not been reported elsewhere. Our aims were the molecular detection and genetic analysis of EV109 from acute childhood respiratory infections in Hungary. Nasopharyngeal aspirates were collected from children under age of 10 years with acute respiratory infections treated in Department of Pulmonology, Kaposi Mór Teaching Hospital, Mosdós, Hungary. Samples were taken from 15 October to 15 May in two respiratory seasons 2005/2006 and 2006/2007. Samples were tested using EV109 specific VP1 primers by RT-PCR method. One (1.1%) of the 92 nasopharyngeal aspirates was positive for EV109 collected from a 2.5-year-old child in January, 2007. The main symptoms were dropping nose, fever (38.1°C), hard cough and wheezing associated with bronchitis and pneumonia. Based upon the VP1 gene region EV109 (L87/HUN/2007, JN900470) has 93% nucleotide identity and identical recombinant pattern to the prototype EV109. This is the first detection of the novel recombinant enterovirus, EV109, in Hungary (in Europe). This study supports the possibility that EV109 is able to cause acute respiratory infections, in addition, it might be plays a part in lower respiratory disease with hospitalization in children.

Detection and follow-up of torque teno midi virus ("small anelloviruses") in nasopharyngeal aspirates and three other human body fluids in children.

Torque teno midi virus/small anellovirus (TTMDV/SAV) is a member of the family Anelloviridae. It has a single-stranded, circular, negative-sense DNA genome. Its pathogenic role in human disease remains to be confirmed. In this study, viral shedding, molecular epidemiology and genetic diversity of TTMDV/SAV were studied in human body fluids. Nasopharyngeal aspirates collected from children with acute respiratory disease were tested by PCR/nested PCR for TTMDV/SAV in two seasons (2005/2006, 2006/2007). Two years later, additional urine, stool, and serum samples and nasopharyngeal aspirates were collected from eight symptomless children for follow-up investigation. Forty-three (46.7%) of the 92 nasopharyngeal aspirates collected contained TTMDV/SAV. High genetic diversity was observed; however, identical sequences were also detected in two patients. The mean age of the infected children was 3 years (1 months-8 years), and 58% of them were female. Co-infection with RSV was detected in 23% of the samples. In a follow-up study, nasopharyngeal aspirates and serum of six (75%), stool samples of four (50%) and urine samples of two (25%) of the eight children were anellovirus-positive. None of the anellovirus sequences were identical in the two collection periods, but identical sequences were detected in different body fluids collected at the same time from the same child. TTMDV/SAVs shedding was detected in four human body fluids. As a consequence, it is possible that generalized infection and fecal/uro-oral transmission of TTMDV/SAV occur. TTMDV/SAVs are frequently present in nasopharyngeal aspirates, although the variants may only be transient agents. Further research is needed to investigate the pathogenesis and pathogenic role of TTMDV/SAV.

[Detection and molecular epidemiology of respiratory syncytial virus type A and B strains in childhood respiratory infections in Hungary]. / A légúti óriássejtes vírus A és B típusának molekuláris kimutatása és epidemiológiája gyermekkori légúti fertozésekben.

UNLABELLED: Human respiratory syncytial virus (hRSV) is one of the major causes of respiratory infection of infants and children worldwide. The molecular epidemiology of hRSV is unknown in Hungary. AIMS: Our aims were the molecular detection and genetic analysis of hRSV from childhood respiratory infections in Hungary. MATERIALS AND METHODS: Nasopharyngeal aspirates were collected from children under the age of 10 years with acute respiratory infections provided by the Pediatric Department of the Hospital for Chest Diseases in Mosdós. Samples were taken from 15 October to 15 May in seasons of 2005/2006 and 2006/2007. The clinical and epidemiological data were collected prospectively. The amplification of the surface fusion glycoprotein (F) and the attachment glycoprotein (G) genes of viral RNA was made by RT-PCR method. PCR-products were sequenced and analyzed by phylogenetic analysis. RESULTS: Nasopharyngeal aspirates of 104 children were examined out of which 23 (22.1%) samples - 16 males (69.6%) and 7 females (30.4%) - (first season: 1/49, 2%; second season: 22/55, 40%) contained hRSV. The hRSV infections were taking place from December to March. The average age was 2.1 years (1 month to 8 years). The leading symptoms were dropping nose, fever, cough and wheezing. Thirty-nine point one percent of the hRSV infected children had underlying disease. Based upon the F region 22 (96%), viruses genetically belonged to type A and 1 (4%) was classified as type B hRSV. Based upon the G region, out of the 11 type A viruses 8 (72.7%) belonged to group GA5 and 3 (27.3%) to group GA2. Viral nucleotide sequence was identical in several cases. CONCLUSIONS: To our knowledge, this is the first report on molecular detection and genetic analysis of the two types (A and B) of hRSV of children under the age of 10 with respiratory infections in Hungary. In winter and spring hRSV is an important cause of childhood respiratory infections, particularly in infants, often requiring hospitalization.

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.

Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial.

PURPOSE: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy. PATIENTS AND METHODS: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm). RESULTS: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities. CONCLUSION: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.

[First detection of human metapneumovirus in a child with respiratory syndrome in Hungary]. / Humán metapneumovírus elso hazai kimutatása gyermekkori légúti fertozésbol.

INTRODUCTION: Human metapneumovirus was identified in 2001 as a respiratory-tract pathogen that has been classified as a new genera in family Paramyxoviridae. AIMS: Molecular detection of human metapneumovirus in Hungary. MATERIALS AND METHODS: Human metapneumovirus was identified in nasopharyngeal aspirate amplification of the viral fusion and nucleocapsid genes by reverse transcription-polymerase chain reaction followed by sequencing and phylogenetic analysis. RESULTS: A 4 years-old girl with chronic respiratory syndrome chronically treated with anti-asthma drugs was admitted to hospital in November 2005 with acute respiratory syndrome and atelectasis. Nasopharyngeal aspirate was negative for common bacteria by culture and for influenza and coronavirus by reverse transcription-polymerase chain reaction. By contrast, specimen was positive by reverse transcription-polymerase chain reaction and was confirmed by sequencing both genes (nucleocapsid and fusion) of human metapneumovirus. Human metapneumovirus (HUN 05-L20) clustered into the subgroup B1 has the closest nucleotide similarity (98%) to JPS03-194 (AY530094) detected in Japan. CONCLUSIONS: Human metapneumovirus contributes as an etiological agent of acute lower and upper respiratory tract infection especially in winter season in children with bronchiolitis, pneumonia or episodes of asthma exacerbation in Hungary, too.

Relationship between breath-hold time and physical performance in patients with cystic fibrosis.

Rehabilitation including physiotherapy is an important part of the treatment used to help improve the quality of life of patients with cystic fibrosis (CF). The aim of this study was to determine the value of the breath-hold time as an index of exercise tolerance in patients with CF. Eighteen patients in different states of CF were included. The breath-hold time was measured in all patients. The fitness level was assessed by means of a progressive exercise test on a cycle-ergometer. During the test, oxygen uptake (VO(2)) and carbon dioxide elimination (VCO(2)) were measured breath by breath. The VO(2) and working capacity (WC) were computed at the anaerobic threshold (AT) and at peak. Duration of breath-hold was 24.7 +/- 2.87 (mean +/- SEM) seconds, varying between 10 and 58. The breath-hold time (BHT) displayed a significant correlation with VO(2) (r = 0.898), WC (r = 0.899) at the AT, and the peak VO(2) (r = 0.895). Regression equations were: VO(2) at the AT (ml/kg) = 5.53 + 0.42 x BHT and WC at the AT (watt/kg) = 0.56 + 0.38 x BHT Our results suggest that the voluntary breath-hold time might be a useful index for prediction of the exercise tolerance of CF patients.

Cost, morbidity, and control of asthma in Hungary: The Hunair Study.

OBJECTIVE: To assess asthma-related morbidity, symptom control, and societal cost of asthmatic patients in Hungary. Secondary objective was to assess the relationship between asthma symptom control and costs incurred. METHODS: Three hundred seventy-eight pediatric asthma patients (6-14 years of age) and 711 adult asthma patients (18-55 years of age) in 19 pulmonary clinics were interviewed by their physicians regarding asthma-related drug therapy and recent (past 2 weeks) asthma morbidity (daytime asthma symptoms, nocturnal symptoms, limitation in daily activities resulting from asthma and asthma exacerbation). Physicians estimated patients' level of asthma control based on the Global Initiative of Asthma guidelines. Direct and indirect costs for asthma-related resources were determined based on patient reported 6 months' data except for drug costs that were based on patient reported 2 weeks of data. All cost data were annualized. RESULTS: Patients in the study were mostly prescribed inhaled controller medications for asthma symptom management (76.2% pediatric and 92.3% adult) during the 2 weeks preceding the survey. Asthma-related morbidity was experienced by 15% of pediatric patients and 30% of the adult patients at least once during the 2 weeks preceding the survey. Physician classified 69% of pediatric patients as having good control, 27.5% as having moderate control, and 2.8% as having poor control of their asthma. In the adult population, 50.7% were classified as having good control, 36.6% as having moderate control, and 12.7% as having poor control. The average total annual costs (direct and indirect costs) per patient were 833 EUR (897 USD) for pediatric patients and 632 EUR (681 USD) for adult patients. In both pediatric and adult patients the total costs were highest for patients with poor asthma control. The total cost per patient increased in the ratios of 1 to 1.4 to 2.4 for pediatric patients and 1 to 1.5 to 2.9 for adult patients with good, moderate, and poor control of asthma, respectively. CONCLUSION: Inhaled corticosteroids was the most frequent treatment prescribed for asthma patients in the study. However, patients reported substantial asthma-related morbidity. Children used more resources than adults, despite being classified as having better control. Patients with poor control of asthma symptoms incurred the highest societal cost, improving patient control may reduce cost to society by 40% or more.

Urinary magnesium excretion in asthmatic children receiving magnesium supplementation: a randomized, placebo-controlled, double-blind study.

The aims of this study were to establish whether a magnesium (Mg) deficit indicated by a decreased urinary excretion exists and to determine whether 12-week oral Mg supplementation affects the Mg status and bronchodilator use in children with stable bronchial asthma. The effects of long-lasting Mg supplementation were investigated in 89 children 4 to 16 years of age with mild or moderate persistent bronchial asthma in a randomized, double-blind, placebo-controlled, prospective study. Each subject received one capsule of Mg citrate per day (= 7 years: 200 mg, > 7 years: 290 mg) or one capsule of placebo containing 260 mg glucose during 12 weeks. Evaluation was performed at 4-week intervals. Venous blood serum total and free Mg and urine Mg levels were determined at the beginning and end of the 12-week period. Parents recorded the number of bronchodilator doses twice daily. A urinary Mg loss (6.81 +/- 3.9 versus 2.79 +/- 1.39 mmol/day, p = 0.01) was observed in the placebo-treated persistent moderate asthmatics. Bronchodilator use was significantly higher after 8 and 12 weeks in the placebo-treated than in the Mg-treated patients with moderate asthma (31.1 +/- 1.8 versus 29.5 +/- 1.2 puffs per patient/4 weeks, p < 0.05, and 31.0 +/- 2.3 versus 29.3 +/- 0.9 puffs per patient/4 weeks, p < 0.05, respectively). Long-lasting Mg supplementation is clearly of benefit in mildly to moderately asthmatic children and is recommended as a concomitant drug in stable asthma.