Balázs Odler

Long time enzyme replacement therapy stabilizes obstructive lung disease and alters peripheral immune cell subsets in Fabry patients

Fabry disease is an X‐linked lysosomal storage disorder, causing accumulation of globotriaosylceramid in different organs. Glycolipids are activators of different immune cell subsets the resulting inflammation is responsible for organ damage. Pulmonary involvement leads to airway inflammation; however, data on severity, as well as the effect of enzyme replacement therapy on lung function parameters and changes in peripheral immune cell subsets on lung involvement are sparse.

Gene polymorphisms as risk factors for predicting the cardiovascular manifestations in Marfan syndrome: Role of folic acid metabolism enzyme gene polymorphisms in Marfan syndrome

Folic acid metabolism enzyme polymorphisms are believed to be responsible for the elevation of homocysteine (HCY) concentration in the blood plasma, correlating with the pathogenesis of aortic aneurysms and aortic dissection. We studied 71 Marfan patients divided into groups based on the severity of cardiovascular involvement: no intervention required (n=27, Group A); mild involvement requiring intervention (n=17, Group B); severe involvement (n=27, Group C) subdivided into aortic dilatation (n=14, Group C1) and aortic dissection (n=13, Group C2), as well as 117 control subjects. We evaluated HCY, folate, vitamin B12 and the polymorphisms of methylenetetrahydrofolate reductase (MTHFR;c.665C>T and c.1286A>C), methionine synthase (MTR;c.2756A>G) and methionine synthase reductase (MTRR;c.66A>G). Multiple comparisons showed significantly higher levels of HCY in Group C2 compared to Groups A, B, C1 and control group (p<0.0001, p<0.0001, p=0.001 and p=0.003, respectively). Folate was lower in Group C2 than in Groups A, B, C1 and control subjects (p<0.0001, p=0.02, p<0.0001 and p<0.0001, respectively). Group C2 had the highest prevalence of homozygotes for all four gene polymorphisms. Multivariate logistic regression analysis revealed that HCY plasma level was an independent risk factor for severe cardiovascular involvement (Group C; odds ratio [OR] 1.85, 95% confidence interval [CI] 1.28-2.67, p=0.001) as well as for aortic dissection (Group C2; OR 2.49, 95%CI 1.30-4.78, p=0.006). In conclusion, severe cardiovascular involvement in Marfan patients, and especially aortic dissection, is associated with higher HCY plasma levels and prevalence of homozygous genotypes of folic acid metabolism enzymes than mild or no cardiovascular involvement. These results suggest that impaired folic acid metabolism has an important role in the development and remodelling of the extracellular matrix of the aorta.

Vitamin D deficiency is associated with impaired disease control in asthma-COPD overlap syndrome patients

Introduction The association between vitamin D and clinical parameters in obstructive lung diseases (OLDs), including COPD and bronchial asthma, was previously investigated. As asthma–COPD overlap syndrome (ACOS) is a new clinical entity, the prevalence of vitamin D levels in ACOS is unknown. Aim Our aim was to assess the levels of circulating vitamin D (25-hydroxyvitamin D [25(OH)D]) in different OLDs, including ACOS patients, and its correlation with clinical parameters. Methods A total of 106 men and women (control, n=21; asthma, n=44; COPD, n=21; and ACOS, n=20) were involved in the study. All patients underwent detailed clinical examinations; disease control and severity was assessed by disease-specific questionnaires (COPD assessment test, asthma control test, and modified Medical Research Council); furthermore, 25(OH)D levels were measured in all patients. Results The 25(OH)D level was significantly lower in ACOS and COPD groups compared to asthma group (16.86±1.79 ng/mL and 14.27±1.88 ng/mL vs 25.66±1.91 ng/mL). A positive correlation was found between 25(OH)D level and forced expiratory volume in 1 second (r=0.4433; P<0.0001), forced vital capacity (FVC) (r=0.3741; P=0.0004), forced expiratory flow between 25% and 75% of FVC (r=0.4179; P<0.0001), and peak expiratory flow (r=0.4846; P<0.0001) in OLD patient groups. Asthma control test total scores and the 25(OH)D level showed a positive correlation in the ACOS (r=0.4761; P=0.0339) but not in the asthma group. Higher COPD assessment test total scores correlated with decreased 25(OH)D in ACOS (r=−0.4446; P=0.0495); however, this was not observed in the COPD group. Conclusion Vitamin D deficiency is present in ACOS patients and circulating 25(OH)D level may affect disease control and severity.

A szisztémás lupus erythematosus pulmonalis manifesztációi

Systemic lupus erythematosus is the most common connective tissue disease that is associated with pulmonary manifestations. Although lupus has the potential to affect any organ, lung involvement is observed during the course of the disease in most cases and it is prognostic for outcome. Pulmonary manifestations in lupus can be classified into five groups based on the anatomical involvement: pleura, lung parenchyma, bronchi and bronchioli, lung vasculature and respiratory muscles can be involved. The most common respiratory manifestations attributable to lupus are pleuritis with or without pleural effusion, pulmonary vascular disease, upper and lower airway dysfunction, parenchymal disease, and diaphragmatic dysfunction (shrinking lung syndrome). In this article the authors summarize lung involvement of lupus, its diagnosis, therapy and prognosis. Orv. Hetil., 2016, 157(29), 1154-1160.

Characteristics of reversible and nonreversible COPD and asthma and COPD overlap syndrome patients: an analysis of salbutamol Easyhaler data

The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70% in chronic obstructive pulmonary disease [COPD]; <80% in asthma) were included (n=121, age: 57.8±17.3 years). Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria) was tested in patients with COPD (n=63) and asthma and COPD overlap syndrome (ACOS; n=12). Forty-six asthmatics served as controls. Reversibility was tested with 400 µg salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland). Demographic data and patients’ perceptions of Easyhaler compared with β2-agonist pressurized metered dose inhalers (pMDIs) were analyzed. American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients. Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P<0.0001). Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P<0.0001). Reversibility was equally often found in smokers as in never-smokers (33% vs 34%). Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients. Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI. Never-smokers and patients with asthma experienced Easy-haler somewhat easier to use than smokers and patients with COPD. In conclusion, a substantial part of patients with COPD or ACOS showed reversibility to salbutamol dry powder inhaler. Nonreversible patients with COPD were characterized by higher weight and body mass index, and a higher FEV1/FVC ratio. Most patients preferred Easyhaler compared with a pMDI.

Asthma-COPD overlap szindróma

Obstructive lung diseases represent a major health problem worldwide due to their high prevalence associated with elevated socioeconomic costs. Bronchial asthma and chronic obstructive pulmonary disease are chronic obstructive ventilatory disorders with airway inflammation, however they are separate nosological entities based on thedifferent development, diagnostic and therapeutic approaches, and prognostic features. However, these diseases may coexist and can be defined as the coexistence of increased variability of airflow in a patient with incompletely reversible airway obstruction. This phenotype is called asthma - chronic obstructive pulmonary disease overlap syndrome. The syndrome is a clinical and scientific challenge as the majority of these patients have been excluded from the clinical and pharmacological trials, thus well-defined clinical characteristics and therapeutic approaches are lacking. The aim of this review is to summarize the currently available literature focusing on pathophysiological and clinical features, and discuss possible therapeutic approaches of patients with asthma - chronic obstructive pulmonary disease overlap syndrome. Orv. Hetil., 2016, 157(33), 1304-1313.