Changes in the Burden of Comorbidities in Patients with COPD and Asthma-COPD Overlap According to the GOLD 2017 Recommendations.

PURPOSE: Comorbidities associated with chronic obstructive pulmonary disease (COPD) affect quality of life and increase mortality. Asthma-COPD overlap (ACO) may express a different profile of comorbidities compared to COPD alone. It is unclear how recent changes in GOLD recommendations affect the profile of comorbidities in COPD and ACO. METHODS: Eight hundred and thirty-four patients with COPD were recruited from 67 Hungarian secondary care outpatient clinics, 469 of them had ACO. Comorbidities were defined by respiratory specialists based on medical history, patient report, and medications. COPD grades were defined according to the old 2016 and the new 2017 GOLD document. Comorbidities were compared along COPD ABCD groups determined by the old and new GOLD. RESULTS: 66 and 72% of the COPD patients in groups C and D (GOLD 2016) were recategorized to groups A and B (GOLD 2017), respectively. There was no difference in the prevalence of disorders along the 2016 GOLD categories except for osteoporosis in ACO (p = 0.01). When the patients were categorized according to the 2017 GOLD criteria, the prevalence of osteoporosis (p = 0.01) was different among the four groups in all COPD patients. Subgroup analysis of non-ACO COPD patients revealed inter-group differences for cardiac arrhythmia (p < 0.01). No alteration was seen in the prevalence of coronary artery disease, hypertension, diabetes, or the total number of comorbidities. CONCLUSION: A significant number of patients are recategorized according to the GOLD 2017 criteria. This change only marginally affects the profile of comorbidities; still this needs to be considered when assessing the patients in daily practice.

Relationship Between Medication Adherence and Health-Related Quality of Life in Subjects With COPD: A Systematic Review.

BACKGROUND: Various aspects of medication adherence and health-related quality of life (HRQOL) have been studied in subjects with COPD. Nevertheless, little is known about the association between these factors. The aim of this study was to undertake a systematic review of the published literature focusing on the relationship between medication adherence and HRQOL in COPD. METHODS: A systematic literature search of English language articles was conducted in April 2013 using MEDLINE. No publication date limits were defined. All of the included studies were assessed for quality. RESULTS: Seven studies were included in the review. Three of the assessed studies found no correlation, and 3 studies described positive and 2 studies reported negative associations between medication adherence and HRQOL. The results indicate that an improved HRQOL may be a trigger for non-adherence in patients with COPD. CONCLUSIONS: The relationship between medication adherence and HRQOL may be dual. The effect of medication adherence on HRQOL might be a consequence of the effectiveness of therapy and the negative effects (ie, side effects, daily life limitation of therapy, social stigma) that it can generate. HRQOL might also influence the patterns of patients' drug use, as an increased HRQOL might trigger non-adherence. The dynamics between adherence and HRQOL might differ over time, as the negative effects of medication non-adherence might become dominant in the long term.

Pitfalls associated with the therapeutic reference pricing practice of asthma medication.

BACKGROUND: Therapeutic reference pricing (TRP) based on the WHO daily defined dose (DDD) is a method frequently employed for the cost-containment of pharmaceuticals. Our objective was to compare average drug use in the real world with DDD and to evaluate whether TRP based on DDD could result in cost savings on maintenance medication and the total direct health expenditures for asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED) in Hungary. METHODS: Real-world data were derived from the Hungarian National Health Insurance Fund database. Average doses and costs were compared between the high-dose and medium-dose SYT and SED groups. Multiple linear regressions were employed to adjust the data for differences in the gender and age distribution of patients. RESULTS: 27,779 patients with asthma were included in the analysis. Average drug use was lower than DDD in all groups, 1.38-1.95 inhalations in both SED groups, 1.28-1.97 and 1.74-2.49 inhalations in the medium and high-dose SYT groups, respectively. Although the cost of SED based on the DDD would be much lower than the cost of SYT in the medium-dose groups, no difference was found in the actual cost of the maintenance therapy. No significant differences were found between the groups in terms of total medical costs. CONCLUSIONS: Cost-containment initiatives by payers may influence clinical decisions. TRP for inhalation asthma drugs raises special concern, because of differences in the therapeutic profile of pharmaceuticals and the lack of proven financial benefits after exclusion of the effect of generic price erosion. Our findings indicate that the presented TRP approach of asthma medications based on the daily therapeutic costs according to the WHO DDD does not result in reduced public healthcare spending in Hungary. Further analysis is required to show whether TRP generates additional expenditures by inducing switching costs and reducing patient compliance. Potential confounding factors may limit the generalisability of our conclusions.

Rate of preterm birth in pregnant women with vitamin E treatment: a population-based study.

OBJECTIVE: Vitamin E is frequently used for prevention/treatment of repeated or threatened abortion and threatened preterm delivery in Hungarian pregnant women, though, internationally this old-fashion method is not recommended. METHODS: The rate of preterm birth of newborns in pregnant women with high dose (estimated daily dose 450 mg) vitamin E treatment or without this treatment was compared in the population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. RESULTS: Of 38,151 newborns with any defect, 2,287 (6.0%) had mothers with vitamin E treatment. Pregnant women with vitamin E treatment had very high rate of threatened abortion (43.6% vs. 15.4%) and high rate of threatened preterm delivery (27.5% vs. 13.4%) compared to pregnant women without vitamin E treatment. Nevertheless, the gestational age at delivery was 0.2 week longer and rate of preterm births was lower in the newborns of pregnant women with vitamin E treatment (6.6% vs. 9.3%; adjusted OR with 95% CI: 0.71, 0.63-0.84). This preterm preventive effect of vitamin E treatment could not be explained by known confounders, though folic acid/multivitamins also reduced the rate of preterm birth. CONCLUSION: The study showed nearly 30% reduction in preterm births of pregnant women with vitamin E treatment.

No association of maternal vitamin E intake with higher risk of cardiovascular malformations in children: a population-based case-control study.

OBJECTIVE: In Hungary, vitamin E is frequently used to prevent repeated or threatened abortion. A previous study showed a higher risk of cardiovascular malformations in the children of pregnant women who had a high vitamin E intake either in their diet or by taking supplements. The objective was to examine this association. METHODS: The Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996, is a large, population-based dataset including 22,843 cases with congenital abnormalities, 38,151 healthy controls matched to the cases, and 834 patient controls with Down syndrome. Vitamin E treatment was compared in the mothers of these children. RESULTS: The mothers of 1418 cases with congenital abnormalities (6.2%), 2267 controls (6.0%) and 43 patient controls (5.2%) had vitamin E treatment during pregnancy. A preliminary comparison of cases and controls showed a higher risk for four congenital abnormality groups, including cardiovascular malformations. However, if only prospectively and medically recorded vitamin E treatments in the prenatal maternity logbook were evaluated during the critical period of different congenital abnormalities, the higher risk for these congenital abnormalities was not found. CONCLUSIONS: The results of this study were based on relatively high-dose vitamin E intake in pregnant women and were not able to confirm the previously reported teratogenic effect of vitamin E.

Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks.

The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate ('folate').

A population-based case-control teratologic study of promethazine use during pregnancy.

Objective of the study was to investigate the teratogenic effect of oral promethazine, a phenothiazine derivate in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities during the years 1980-1996. Of 22,843 cases with 25 congenital abnormalities, 3648 (16.0%) were born to mothers treated orally with promethazine during pregnancy. Of 38,151 matched population controls without congenital abnormalities, 6025 (15.8%) had mothers with promethazine treatment during the study pregnancy. Of 834 malformed controls (Down syndrome), 142 (17.0%) had mothers with treatment of promethazine in the study pregnancy. The case-all matched population controls analysis showed a higher rate of cleft lip+/-cleft palate (adjusted OR with 95% CI: 1.5, 1.1-2.0) and poly/syndactyly (OR with 95% CI: 1.3, 1.0-1.8) after promethazine treatment during the 2nd and 3rd months of gestation. However, these risks were explained by recall bias, because these associations were not confirmed after the evaluation of only medically recorded promethazine uses. The comparison of promethazine treatment between 25 congenital abnormality groups and malformed controls did also not show any risk. Thus, the overall evidence from analysis presented did not suggest that clinical doses of promethazine increased the rate of congenital abnormalities in humans.

No teratogenic effect of prenoxdiazine: a population-based case-control study.

The objective of this study was to investigate the human teratogenic potential of oral prenoxdiazine treatment during pregnancy. The analysis of cases with congenital abnormalities and their matched controls without congenital abnormalities was performed in the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Of the 22,843 pregnant women who had offspring with congenital abnormalities, 158 (0.7%) were treated with prenoxdiazine. Of the 38,151 pregnant women who had babies without any defects in the study period (control group), 226 (0.6%) were treated with prenoxdiazine (adjusted prevalence odds ratio, 1.0; 95% confidence interval, 0.8-1.3). The comparison of cases and their matched controls did not show a significantly higher rate of prenoxdiazine treatment during the second and third months of gestation in the total (adjusted prevalence odds ratio, 1.4; 95% confidence interval, 0.9-2.2) or in any group of congenital abnormalities. Treatment with prenoxdiazine during pregnancy did not have any teratogenic risk to the fetus. Thus, prenoxdiazine treatment in pregnant women with an unproductive cough may be beneficial.

Population-based case-control study of allergic rhinitis during pregnancy for birth outcomes.

OBJECTIVE: Allergic rhinitis is frequent in women of childbearing age including pregnancy. The present study aimed to estimate the effect of maternal allergic rhinitis on birth outcomes, in particular congenital abnormalities, preterm birth and low birthweight newborns. STUDY DESIGN: Analysis of the population-based data of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. RESULTS: The evaluation of data did not reveal any teratogenic potential of allergic rhinitis and indeed a lower prevalence of total congenital abnormalities was found. In addition, a protective effect could be observed for preterm birth due to longer gestational age (adjusted t=2.97, p=0.003). CONCLUSION: Allergic rhinitis is not risk factor for pregnant women.

A population-based case-control study on the effect of bronchial asthma during pregnancy for congenital abnormalities of the offspring.

Bronchial asthma is one of the most common maternal diseases complicating pregnancy. We assessed the risks of congenital abnormalities in a case-control population-based analysis using the dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of the 22,843 cases with congenital abnormalities, 511 (2.2%) had mothers with bronchial asthma, while of the 38,151 matched control subjects without congenital abnormalities 757 (2.0%) had mothers with bronchial asthma (unadjusted prevalence odds ratios [POR] 1.2; 95% CI: 1.0-1.3). In all mothers with bronchial asthma, a higher incidence of respiratory tract infections and higher drug intake could be observed. In the case group of medically recorded bronchial asthma, a slightly increased risk for club foot has been revealed. However, this weak association could be explained by the higher proportion of preterm births in this group. The main limitation of the analysis was that at the time of data collection only a small proportion of pregnant mothers were using anti-asthma medications recommended by the actual guidelines.

[Tuberculosis due to multidrug resistant Mycobacterium tuberculosis Beijing genotype identified by DNA fingerprinting: the first case identified in Hungary]. / DNS ujjlenyomat-vizsgálattal azonosított Beijing genotípusú Mycobacterium tuberculosis okozta multidrog rezisztens tuberculosis: az elso Magyarországon igazolt eset.

In a 28 years old Mongolian woman in whom pulmonary tuberculosis was diagnosed a poly- and multidrug (isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin) resistant Mycobacterium tuberculosis was isolated from sputum in 2002. Since the patient was from a country with high tuberculosis incidence it was conceivable that she had been infected by a strain with primary resistance in Mongolia. In order to confirm the origin of the strain an IS6110-based DNA fingerprint test was performed on the isolate. The assay revealed that the isolated M. tuberculosis strain belonged to the so-called Beijing family which was never detected in Hungary before.

Conventional and molecular epidemiology of tuberculosis in homeless patients in Budapest, Hungary.

In Hungary the incidence of tuberculosis among the homeless population was 676 per 100,000 in 2002. Sixty-nine percent (140 patients) of all homeless tuberculosis patients were notified in Budapest (the capital). Therefore, a retrospective study that included 66 homeless tuberculosis patients notified in Budapest in 2002 was conducted to determine the rate of recent transmission of the disease and medical risk factors and to identify transmission pathways by means of conventional and molecular epidemiologic methods. IS6110 DNA fingerprinting revealed that 71.2% of the isolates could be clustered. Thirty-four (51.5%) patients belonged to five major clusters (size, from 4 to 11 individuals), and 13 (19.7%) belonged to six smaller clusters. Additional analysis of patient records found that 2 (18%) of the 11 patients in cluster A, 3 (37.5%) of the 8 patients in cluster B, and 2 (33%) of the 6 patients in cluster C were residents of the same three homeless shelters during the diagnosis of tuberculosis. Review of the database of the National Tuberculosis Surveillance Center (NTSC) revealed that 21.2% of the cases have not been reported to the NTSC. These findings indicate that the screening and treatment of tuberculosis among the homeless need to be strengthened and also warrant the review of environmental control steps in public shelters. Improvement of adherence of clinicians to surveillance reporting regulations is also necessary.

[Chronic necrotizing pulmonary aspergillosis in an immunocompromised patient]. / Krónikus nekrotizáló pulmonalis aspergillosis csökkent immunitású betegben.

A case with chronic necrotizing pulmonary aspergillosis that was mimicking the radiomorphology of malignant tumor was reported. The patient was admitted to hospital with progression of a left upper lobe infiltrate which was known and under regular observation for 8 years, and haemoptoe. Computer tomography scan showed a spiculated abnormality in the left upper lobe with mediastinal lymphadenomegaly. Based on this finding pulmonary malignancy was suspected and, therefore, the patient was referred to surgical intervention. The post surgical histology revealed aspergillus in the specimen. Since signs of vascular invasion could not be detected microscopically and the disease developed in immunocompromised patient (due to diabetes mellitus and long term steroid treatment) the clinical condition was determined as chronic necrotizing aspergillosis. It is very likely that the pathogen infected the patient during his daily work in a bakery. The present paper also summarizes the clinical aspects, differential diagnosis and therapy of different forms of pulmonary aspergillosis with emphasis on chronic necrotizing pulmonary aspergillosis.

Different gender-associated genotype risks of Wegener's granulomatosis and microscopic polyangiitis.

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are systemic small vessel vasculitides associated with ANCA (AAV). Predominant Th1 and Th2 cytokine patterns have been reported for WG and MPA, respectively. Consequently, genotypes suppressing Th1 responses or augmenting Th2 responses may be more frequent in MPA than in WG. Transforming growth beta1 (TGF-beta1) and interleukin-10 (IL-10) genes may modify the course of vasculitis. Therefore, we investigated associations between genotype frequencies of functional polymorphisms of these cytokine genes and clinical manifestations in AAV. One hundred sixty-one AAV patients and 153 healthy blood donors were genotyped for the biallelic polymorphism in codon 25 of the TGF-beta1 gene and the biallelic polymorphism at position -1082 of the IL-10 gene. No difference was found for TGF-beta1 codon 25 polymorphism between control and patient groups. In contrast, a significant shift toward the homozygous AA genotype of the IL-10 (-1082) polymorphism was found in WG (25%, p<0.005) and MPA patients (39%; p<0.00001) compared to controls (10.5%). Furthermore, in MPA the AA homozygous genotype was significantly more frequent in females (62.5%) compared to males (20%, p<0.05). A contribution of the TGF-beta1 codon 25 polymorphism to the susceptibility-defining genetic backgrounds of AAV appears unlikely. In contrast, our findings suggest a role of the enhanced IL-10 (-1082) PM in WG and MPA with a significant gender difference in MPA.

[Treatment of bronchial asthma in pregnancy]. / Az asthma bronchiale kezelése terhességben.

The prevalence of bronchial asthma, similarly to the normal population, is also increasing among pregnant women. Asthma a chronic inflammatory disease of the airways, is one of the most common medical problems that can complicate pregnancy. The cornerstone of asthma management in pregnancy is to implement such treatment strategies that can maintain normal maternal pulmonary function and prevent fetal complications. The aim of the present article is to summarize the recent publications and guidelines on the safety and efficacy issues of asthma treatment during pregnancy.

A Possible Association between Oral Aminophylline Treatment during Pregnancy and Skeletal Congenital Abnormalities.

OBJECTIVE: To study the human teratogenic potential of oral aminophylline treatment during pregnancy. DESIGN AND SETTING: The analysis of each case and its matched controls, as well as comparison of population or patient controls and cases with 25 groups of congenital abnormalities in the population-based data set of the large Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. STUDY PARTICIPANTS: 38 151 pregnant women who had newborn infants without any congenital abnormalities (population control group), 22 843 pregnant women who had newborn infants or fetuses with congenital abnormalities, and 834 patient controls with Down's syndrome. MAIN OUTCOME MEASURES: Prevalence of aminophylline use in cases with the 25 congenital abnormality groups compared with population control and patient control groups. RESULTS: The prevalence of oral aminophylline treatment during pregnancy was similar in the case group (1374 pregnant women; 6.0%) and the population control group (2284 pregnant women; 6.0%) [crude prevalence odds ratio (POR) 1.0, 95% confidence interval (CI) 0.9-1.1], while it was higher in the patient control group (55 pregnant women; 6.6%). Comparisons of total population or patient control groups and cases with the 25 different congenital abnormality groups, as well as analysis of cases and their matched controls, indicated an association between aminophylline use and congenital abnormalities of the musculoskeletal system (crude POR 5.0, 95% CI 1.4-18.4, adjusted POR 4.7, 95% CI 1.3-17.2 for aminophylline treatment during the second through third months of gestation; crude POR 1.5, 95% CI 1.0-2.2, adjusted POR 1.5, 95% CI 0.9-2.2 for aminophylline treatment during the entire pregnancy), particularly pectus excavatum/carinatum (3.5 times excess). There was a possible association between aminophylline and clubfoot and posterior cleft palate. These findings may be connected with recall bias, although this bias was restricted by the evaluation of maternal drug use only during the critical period of the above congenital abnormalities and by evaluating medically recorded aminophylline treatment, as well as by the use of patient controls. CONCLUSION: Our findings and previous animal investigations can only be regarded as a signal for the possible association between oral treatment with aminophylline during pregnancy and some congenital abnormalities of the skeletal system.

Differences in the genetic background of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus.

OBJECTIVES: According to the recent classification of diabetes mellitus the Latent Autoimmune Diabetes in Adults (LADA) belongs to the group of type 1 autoimmune diabetes, as a slowly progressive form. Our aim was to determine (i) the prevalence of HLA-DRB1 and DQB1 genotypes, and (ii) to determine the tumor necrosis factor (TNF) alpha promoter polymorphism at position -308 (the G-->A substitution, designated the TNF2 allele) in patients with type 1 diabetes and with LADA compared with the healthy population. METHODS: The major histocompatibility complex (MHC) II genotypes and the TNF alpha promoter polymorphism were determined by PCR method. We examined 69 type 1 diabetic and 42 LADA patients. As control samples of 336 cadaver kidney donors and 138 volunteers were used. RESULTS: Both type 1 diabetes mellitus and LADA were positively associated with the DRB1*04-DQB1*0302 (DR4/DQ8) haplotype (P=0.00001, and P=0.0005, respectively), and negatively associated with the DRB1*11-DQB1*0301 (DR11/DQ7) haplotype (P=0.00006, and P=0.007, respectively) compared with control population. There were differences between the two disease entities in the frequency of the DRB1*03-DQB1*02 (DR3/DQ2) haplotype (P=0.00008 vs. P=0.177) compared with control group. The presence of the TNF2 allele was significantly lower in LADA than type I diabetes (P=0.022) or control group (P=0.017). CONCLUSION: Our findings indicate that there are marked differences in the genetic background of type 1 diabetes and LADA. The low presence of TNF2 allele (known to be associated with high amount of TNF alpha production) in LADA could be one of the factors responsible for the relatively slow progression.