[Show abstract][Hide abstract] ABSTRACT: The number of patients with obstructive airway disease has been increasing worldwide. The delivery of aerosol drugs through the respiratory system has become a central element in the management of asthma and chronic obstructive pulmonary disease (COPD). The aim of this study was to validate and apply a stochastic whole respiratory tract deposition model in order to characterize airway deposition distribution of two different marketed drugs delivered in form of dry powders (Seretide® Diskus® and Symbicort® Turbuhaler®), and to analyze the possibility of computerized drug delivery optimization in the future. Spirometry measurements on 17 adult volunteers have been performed. Relationships between breathing parameters measured during diagnostic spirometry and those characterising breathing during drug administration through Diskus® and Turbuhaler® inhalers have been derived. The doses deposited in different anatomical regions of the respiratory tract and airway generation number specific deposited doses have been computed for the participating individuals based on both MMAD (mass median aerodynamic diameter) and detailed size distribution of the two drugs. Although regional deposited doses were not very different in the two cases, airway generation number specific deposition distributions were sensitive to this input parameter, indicating the need for the whole size distribution when modelling airway deposition of aerosol drugs. Significant intersubject variability in terms of oropharyngeal, bronchial and acinar deposited doses have been found. The results highlight the necessity for and open the possibility of simulation assisted customized drug selection in the future.
Aerosol and Air Quality Research 11/2015; 15(6):2466-2474. DOI:10.4209/aaqr.2015.03.0144 · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of COPD 09/2015; 10(1):2017-2025. DOI:10.2147/COPD.S91654 · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the last few decades the number of patients suffering from asthma has increased both worldwide and in Hungary. The use of aerosol therapy in the treatment of asthma is widespread. Therapeutic aerosol delivery is the most efficient, when the right amount of the appropriate drug is delivered to the right location in the respiratory system. However, achieving this goal is a complex task, which opens up a wide spectrum of research and development areas, including the study of transport and deposition distributions of inhaled aerosols within the lungs. The main objective of the present work was the quantification the deposition distribution of three selected commercially available ICS-LABA drug combinations in the respiratory system and the planning of the directions of aerosol drug delivery optimisation in the respiratory system by the application of measurements and complex numerical models. Spirometry measurements have been performed on seventeen volunteers, and then the corresponding spirometry data were measured through the selected inhalation devices which have different resistances. Relationships between breathing parameter values measured during diagnostic spirometry and those characterising breathing during drug administration through inhalers have been established. Spirometry test values served as input data for the modelling of regional deposition distributions of the selected aerosol drugs. The Stochastic Lung Model has been applied to quantify the amount of medication deposited on the target area and out of it. Based on our computational results, the efficiency of the deposition of each selected aerosol drug was patient specific, which opens the possibility of simulation assisted customized drug selection. The appropriateness of the different drugs and breathing modes proved to be quite sensitive to the selection of the target area. Our results highlight the possibility of an individualised and optimised aerosol drug delivery and treatment of lung diseases in the future. In addition, a new method was elaborated to decide whether a selected patient is able or not to produce appropriate inhalation flow rate for the use of a given dry powder inhaler.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease involving several organs, including the lungs. Previous results confirmed changes of peripheral T cell subsets in lupus patients; however no data are available about their possible relationship with pulmonary involvement.
To determine pulmonary manifestations and potential relationship in changes of peripheral CD4+ T cell subsets.
Patients with SLE (N=28) were enrolled in complex pulmonary examination. Patients were divided into groups with pleuropulmonary manifestations (SLEpulm N=13 age: 44.9±3.3 years, female: male=11:2) or without (SLEc N=15 age: 27.2±3.7 years, female: male=12:3). Peripheral blood was taken for T helper (Th)1, Th2, Th17, CD4+CD25hi+ and regulatory T (Treg: CD4+CD25hi+CD127-) cell analysis from SLE patients and healthy volunteers (controls, N=40).
SLEpulm patients were older, had more pulmonary symptoms and significantly decreased pO2 as compared to SLEc group. Ventilatory disorder was present in 92% of SLEpulm patients, with significantly decreased lung volumes, signs of airway involvement and decrease in DLco. Significant increase in Th1/Th2, while decrease in Th17/Treg ratios was present in all SLE compared to controls. In SLEpulm CD4+CD25hi+ subset without changes in Treg number was significantly increased as compared to SLEc and this subgroup of T cell showed significant positive correlation with dynamic lung function parametes and DLco (p<0.05).
In lupus patients pleuropulmonary manifestations are prevalent and lung function and blood gas measurements should be regularly performed in the daily clinical assessment. Significant increase of activated CD4+CD25hi+ T cells, but nor Treg is associated with decreased lung function parameters in SLEpulm patients.
Respiratory medicine 05/2014; 108(5). DOI:10.1016/j.rmed.2014.02.006 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Uncontrolled asthma is a risk factor for pregnancy-related complications. Hyaluronic acid (HA), a potential peripheral blood marker of tissue fibrosis in various diseases, promotes eosinophil survival and plays a role in asthmatic airway inflammation as well as in physiological processes necessary to maintain normal pregnancy; however the level of circulating HA in asthma and asthmatic pregnancy is unknown. We investigated HA levels in asthmatic patients (N = 52; asthmatic pregnant (AP) N = 16; asthmatic non-pregnant (ANP) N = 36) and tested their relationship to asthma control. Serum HA level was lower in AP than in ANP patients (27 [24.7-31.55] vs. 37.4 [30.1-66.55] ng/mL, p = 0.006); the difference attenuated to a trend after its adjustment for patients' age (p = 0.056). HA levels and airway resistance were positively (r = 0.467, p = 0.004), HA levels and Asthma Control Test (ACT) total score inversely (r = -0.437, p = 0.01) associated in ANP patients; these relationships remained significant even after their adjustments for age. The potential value of HA in the determination of asthma control was analyzed using ROC analysis which revealed that HA values discriminate patients with ACT total score ≥20 (controlled patients) and <20 (uncontrolled patients) with a 0.826 efficacy (AUC, 95% CI: 0.69-0.97, p = 0.001) when 37.4 ng/mL is used as cut-off value in ANP group, and with 0.78 efficacy (AUC, 95% CI: 0.65-0.92, p = 0.0009) in the whole asthmatic cohort. In conclusion circulating HA might be a marker of asthma control, as it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease of HA level in pregnancy may be the consequence of pregnancy induced immune tolerance.
PLoS ONE 04/2014; 9(4):e94678. DOI:10.1371/journal.pone.0094678 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2872096831190851.
Castleman disease (CD), described as a heterogeneous lymphoproliferative disorder, can be divided into different subtypes according to clinical appearance (unicentric and multicentric form) and histopathological features (hyaline vascular, plasma cell, mixed type, human herpesvirus 8–associated and multicentric not otherwise specified). Unicentric CD is known to be usually of the hyaline vascular variant, plasma cell and mixed type of this form are quite uncommon. Malignancies are mainly associated with the multicentric form. We report a rare case of unicentric mixed variant CD evolving into intrabronchial, extramedullary plasmacytoma.
Intrabronchial mass with consequential obstruction of the left main bronchus, left lung atelectasis and mediastinal lymphadenomegaly was detected by chest CT in our patient suffering from cough and hemoptysis. Pulmonectomy was performed, histopathological and immunhistochemical analysis of lymph nodes revealed mixed type of CD with interfollicular monotypic plasma cell proliferation. The intrabronchial mass consisted of monotypic plasma cells confirming plasmacytoma. Systemic involvement was not confirmed by further tests.
Although malignancies more often present in multicentric CD that usually belongs to the plasma cell subtype, this case confirms the neoplastic potential of the rarest, unicentric mixed variant of CD.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate patients' inhaler competence and satisfaction with the Easyhaler(®) dry powder inhaler.
Two open, uncontrolled, non-randomised studies.
Real life based on patients attending 56 respiratory clinics in Hungary.
Patients with asthma or chronic obstructive pulmonary disease (COPD) (n = 1016).
In a 3-month study, adult patients (age range 18-88 years; n = 797) received twice-daily inhalations of formoterol via Easyhaler(®), and in a consequential study (from one visit to another, with 3-12 months in-between) children and adolescents (age range 4-17 years; n = 219) received salbutamol via Easyhaler(®) as needed.
Control of six Easyhaler(®) handling steps and patients' satisfaction with Easyhaler(®) based on questionnaires.
Correct performances (minimum and maximum of the six steps) were noticed after one demonstration in 92-98 % of the adults, 87-99 % of the elderly, 81-96 % of the children and 83-99 % of the adolescents. These figures had markedly increased at the last visit. Repeat instructions were necessary in 26 % of the cases. Investigators found Easyhaler(®) easy to teach in 87 % of the patients and difficult in only 0.5 %. Patients found Easyhaler(®) easy to learn and use, and the patients' (and parents') satisfaction with the inhaler was very high. Lung function values [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)] improved statistically significantly during the studies, indicating good inhaler competence and treatment adherence.
Investigators found Easyhaler(®) easy to teach and patients found it easy to use, and their satisfaction with the device was high.
[Show abstract][Hide abstract] ABSTRACT: Small airways disease plays an important role in the pathogenesis of asthma, but assessment of small airways impairment is not easy in everyday clinical practice. The small airways can be examined by several invasive and noninvasive methods, most of which can at present be used only in the experimental setting. Inhalers providing extrafine inhaled corticosteroid particle sizes may achieve sufficient deposition in the peripheral airways. Many studies have reported the beneficial effects of extrafine inhaled corticosteroids on inflammation, ie, on dysfunction in both the central and distal airways in asthmatics, and there are some data on asthma phenotypes in which the small airways seem to be affected more than in other phenotypes, including nocturnal asthma, severe steroid-dependent or difficult-to-treat asthma, asthma complicated by smoking, elderly asthmatic patients and/or patients with fixed airflow obstruction, and asthmatic children. The relevant randomized controlled clinical trials indicate that the efficacy of extrafine and nonextrafine inhaled corticosteroid formulations is similar in terms of primary endpoints, but there are certain clinically important endpoints for which the extrafine formulations show additional benefits.
Journal of Asthma and Allergy 06/2013; 6(6):69-80. DOI:10.2147/JAA.S25415
[Show abstract][Hide abstract] ABSTRACT: Asthma has a high burden of morbidity if not controlled and may frequently complicate pregnancy, posing a risk for pregnancy outcomes. Elevated plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is related to a worse prognosis in many conditions such as infectious, autoimmune, or pregnancy-related diseases; however the value of suPAR in asthma and asthmatic pregnancy is unknown. The present study aimed to investigate the suPAR, CRP and IL-6 levels in asthma (asthmatic non-pregnant, ANP; N = 38; female N = 27) and asthmatic pregnancy (AP; N = 15), compared to healthy non-pregnant controls (HNP; N = 29; female N = 19) and to healthy pregnant women (HP; N = 58). The relationship between suPAR levels and asthma control was also evaluated. The diagnostic efficacy of suPAR in asthma control was analyzed using ROC analysis. IL-6 and CRP levels were comparable in all study groups. Circulating suPAR levels were lower in HP and AP than in HNP and ANP subjects, respectively (2.01 [1.81-2.38] and 2.39 [2.07-2.69] vs. 2.60 [1.82-3.49] and 2.84 [2.33-3.72] ng/mL, respectively, p = 0.0001). suPAR and airway resistance correlated in ANP (r = 0.47, p = 0.004). ROC analysis of suPAR values in ANP patients with PEF above and below 80% yielded an AUC of 0.75 (95% CI: 0.57-0.92, p = 0.023) and with ACT total score above and below 20 an AUC of 0.80 (95% CI: 0.64-0.95, p = 0.006). The cut-off value of suPAR to discriminate between controlled and not controlled AP and ANP was 4.04 ng/mL. In conclusion, suPAR may help the objective assessment of asthma control, since it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease in circulating suPAR levels detected both in healthy and asthmatic pregnant women presumably represents pregnancy induced immune tolerance.
PLoS ONE 04/2013; 8(4):e60697. DOI:10.1371/journal.pone.0060697 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous experimental data suggest that steroids might have protective effects during hypoxic/ischemic injury of various organs. In this study, the association between dexamethason (Dexa) treatment and the anti-apoptotic SGK-1 was tested in ischemic renal injury. In vitro, HK-2 cells were exposed to 24 h hypoxia, and the effect of Dexa incubation on SGK-1 expression / activation and on cell death was studied. In an in vivo rat model of unilateral renal IR, animals were treated with Dexa, and serum renal function parameters, tissue injury and SGK-1 expression and localization were examined after different reperfusion times (2 h, 4 h and 24 h). Dexa at a dose of 2 mg/L exerted a protective effect on cell survival assessed by LDH release and vital staining paralleled by marked up-regulation of SGK-1. In rats, 2 mg/kg Dexa treatment 24 h prior to ischemia resulted in less severe tissue injury and ameliorated urea nitrogen levels 24 h after reperfusion. Furthermore, SGK-1 expression and phosphorylation were higher in Dexa animals demonstrated by Western blot and immunofluorescence technique. Our results provide novel data on the signalling mechanism of Dexa under hypoxia / ischemia and further support that Dexa emerges as an attractive pharmacological agent for the prevention of ischemic injury.
[Show abstract][Hide abstract] ABSTRACT: Asthma is a common chronic disease complicating pregnancy with a risk for perinatal complications. Control of airway inflammation in the asthmatic pregnancy improves pregnancy outcomes. Our aim was to evaluate pH of exhaled breath condensate (EBC), a non-invasive method for the assessment of asthmatic airway inflammation, in healthy and asthmatic pregnancies.
Hungarian university clinics.
Seventeen healthy pregnant women, 21 asthmatic pregnant women, 23 healthy non-pregnant women and 22 asthmatic non-pregnant women.
EBC samples were collected using a portable condenser, EBC pH was measured after argon deaeration.
EBC pH (mean ± SD) of healthy non-pregnant and asthmatic non-pregnant women was similar (7.75 ± 0.27 vs. 7.54 ± 0.57; p = 0.118), probably indicating an optimal control of airway inflammation in asthmatic women. On the other hand, EBC pH was higher in healthy pregnant women compared with healthy non-pregnant women (8.02 ± 0.43 vs. 7.75 ± 0.27; p = 0.017). Higher EBC pH accompanying healthy pregnancy was absent in asthmatic pregnant patients whose EBC pH was lower (7.65 ± 0.38) than that of healthy pregnant women (p = 0.006), and it was similar to that in asthmatic and healthy non-pregnant women (p = 0.470 and p = 0.300, respectively). The EBC pH in asthmatic pregnant women correlated positively with birthweight (r = 0.49, p = 0.047) and negatively with forced vital capacity (r = 0.45, p = 0.039). EBC pH was not related to blood pH.
EBC pH is higher in healthy pregnant women but not in asthmatic pregnant women compared with data from healthy non-pregnant women, indicating that oxidative inflammatory processes induced by asthma may compromise the regulatory mechanisms causing alkaline pH in the airways during pregnancy.
[Show abstract][Hide abstract] ABSTRACT: The casual and severity distribution of allergic rhinitis (AR) in Hungary is unknown.
The aim of this survey was to evaluate symptom perception, disease severity, concomitant asthma frequency and the impact of AR on everyday life activities in a cross-sectional, multicenter study in Hungary under the supervision of Hungarian Respiratory Society.
Data were recorded by 933 AR patients (65.93% women) and their treating specialists. The perceptions of patients regarding the symptoms (nasal, ocular and others) of AR and its severity, together with its impact on everyday life were assessed. Physicians recorded data regarding the diagnosis and severity of AR, and comorbidities.
52.5% of patients suffered from seasonal AR, 35.1% from perennial AR. A large proportion of patients had moderate to severe disease (MS-AR) (57.34%), persistent disease (98.0%) and concomitant asthma (53.32% in the mild, 57.52% in the MS-AR group). MS-AR was more frequent among women. Despite the treatment used, in MS-AR the proportions of patients reporting moderate to severe rhinorrhoea, nasal obstruction, ocular itching/redness, watering, itchy throat and sneezing were as high as 52.0%, 54.0%, 33.8%, 26.5%, 44.0% and 31.2%, respectively. Overall, there was a poor agreement between disease severity reported by patients and specialists. The adherence to oral antihistamines and intranasal corticosteroids was found to be between 50 and 65%; mostly depending on the dosage form.
AR remains a significant health problem in Hungary because of the burden of symptoms, high rate of concomitant asthma and the significant proportion of MS-AR affecting general well being.
[Show abstract][Hide abstract] ABSTRACT: Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair patients' quality of life and compromise the effectiveness of chemotherapy. Most side effects of chemotherapy are preventable or treatable with optimal supportive care which enhances success in patient care and treatment. The aim of this review is to summarize the most important conditions that may be associated with combined chemotherapy of lung cancer from the practical point of view.
[Show abstract][Hide abstract] ABSTRACT: Asthmatic inflammation during pregnancy poses a risk for maternal and fetal morbidities. Circulating T cell immune phenotype is known to correlate with airway inflammation (detectable by fractional concentration of nitric oxide present in exhaled breath (FENO)) in non-pregnant allergic asthmatics. The aim of this study was to assess the relationship of peripheral T cell phenotype to FENO and clinical variables of asthma during pregnancy.We examined 22 pregnant women with allergic asthma in the 2nd/3rd trimester. The prevalence of Th1, Th2, regulatory T (Treg) and natural killer (NK) cell subsets was identified with flow cytometry using cell-specific markers. FENO, Asthma Control Test (ACT) total score and lung function were evaluated.Peripheral blood Th1, Th2, Treg, and NK cell prevalence were not significantly correlated to airway inflammation assessed by FENO in asthmatic pregnant women (all cells p > 0.05; study power > 75%). However, an inverse correlation was detected between Th2 cell prevalence and ACT total scores (p = 0.03) in asthmatic pregnancy.Blunted relationship between T cell profile and airway inflammation may be the result of pregnancy induced immune tolerance in asthmatic pregnancy. On the other hand, increased Th2 response impairs disease control that supports direct relationship between symptoms and cellular mechanisms of asthma during pregnancy.
[Show abstract][Hide abstract] ABSTRACT: Solid organ transplantation is the standard of care for selected patients with severe vital organ dysfunction. The need for immunosuppression to prevent organ rejection is a common characteristic of recipients. Immunosuppression increases the risk of infections, especially with low virulence opportunistic pathogens. Infections following solid organ transplantation mainly affect the lungs and the airways. Establishing the diagnosis includes a wide spectrum of pulmonary diagnostics, high standard microbiological analysis and various imaging methods. With the improvement of treatment options, the number of kidney, liver, heart and lung transplant recipients is increasing and, therefore, more and more physicians may meet pulmonary complications in these patients.
Orvosi Hetilap 06/2012; 153(23):899-903. DOI:10.1556/OH.2012.29395
[Show abstract][Hide abstract] ABSTRACT: The inducible heat shock protein (HSP)72 plays a central role in antitumor immunomodulation. HSP72 expression was assessed on tumor samples of 43 patients with advanced and metastatic small cell lung cancer (SCLC) by immunohistochemistry and HSP72 [HSPA1B A(1267)G] polymorphism was determined. HSP72 expression of SCLC cells was significantly decreased in GG as compared to cells of AA or AG genotype patients, and was associated with significantly shorter survival in GG patients as compared to carriers of the A allele. Decreased HSP72 expression of SCLC cells associated with HSP72 GG genotype is a negative prognostic factor for survival in SCLC patients.
Cancer Investigation 04/2012; 30(4):317-22. DOI:10.3109/07357907.2012.657815 · 2.22 Impact Factor