Władysław Pierzchała

Efficacy and Safety of Indacaterol, a New 24-hour β 2-Agonist, in Patients with Asthma: A Dose-Ranging Study

Background. Indacaterol is a new once-daily inhaled β2-agonist in clinical development for asthma as a component of a fixed-dose combination with an inhaled corticosteroid. Objectives. To investigate the efficacy and safety of indacaterol in patients with chronic persistent asthma. Methods. A total of 115 patients were randomized in a double-blind, incomplete-block cross-over design to sequences of four 7-day treatment periods (separated by 7-day washouts) with indacaterol 100, 200, 300, 400, or 600 μ g or placebo, once daily, via single-dose dry-powder inhaler. After the fourth washout, patients received 1 day of open-label formoterol 12 μ g twice daily. Forced expiratory volume in 1 second (FEV1) was measured for 24 hours post-dose on days 1 and 7. Results. For standardized (with respect to time) FEV1 area under the curve at 22 to 24 hours (AUC22–24h) on day 1, indacaterol doses ≥200 μ g were superior to placebo (p < 0.05) and similar or greater than formoterol 12 μg twice daily. By day 7, mean differences from placebo in FEV1 standardized AUC22–24h were 0.08, 0.16, 0.15, 0.11, and 0.16 L for indacaterol 100, 200, 300, 400, and 600 μg, respectively (all p < 0.05 vs. placebo). Mean FEV1 for indacaterol doses ≥ 200 μg on day 7 was higher than placebo (p < 0.05) pre-dose and at all post-dose time points. AEs were generally mild in severity; no serious AEs occurred. No clinically meaningful differences were observed between treatments in any safety assessments. Conclusions. Once-daily indacaterol demonstrated sustained 24-hour bronchodilator efficacy, with similar efficacy on days 1 and 7, and was generally well tolerated.

Short-term continuous positive airway pressure therapy reverses the pathological influence of obstructive sleep apnea on blood rheology parameters

Our aim was to analyze rheological properties of blood and plasma in patients (n=31) with obstructive sleep apnea (OSA) before and after five nights of continuous positive airway pressure (CPAP) therapy as compared with a well-matched control group (n=19). Rheology measurements included blood viscosity, plasma viscosity, erythrocyte elongation and erythrocyte deformability variables specific to the aggregation process. The mean whole blood viscosity of the OSA groups was 18.6% higher than that of the control group (P<0.001), plasma viscosity was 7.2% higher (P<0.001), and the blood count was 6% higher (P<0.001). The corrected viscosity of the OSA group was elevated 6.6% (P<0.05) and the aggregation index was 9.3% higher (P<0.05) relative to the control group. Aggregation half-time of the OSA group was 23.5% shorter than that of the control group (P<0.05). Following CPAP therapy, the rheological variables of the OSA group were significantly reduced: whole blood viscosity was 10.5% lower (P<0.001), plasma viscosity was 4.1% lower (P<0.05), corrected blood viscosity was 4.8% lower (P<0.05), and the aggregation index was 7% lower (P<0.05), while the aggregation half-time was increased 25.4% (P<0.05). There were significant correlations between rheologic and polysomnographic variables for the OSA group. Therefore, five consecutive nights of CPAP therapy improved blood rheological properties in patients with OSA. These findings may help to determine cardiovascular prognoses in these patients.

Quality of life protocol in the early asthma diagnosis in children

Asthma is considered an important problem in children and influences on their everyday functioning. This study was concerned with the impact of asthma on the health‐related quality of life (HRQOL) of newly recognized pediatric asthma patients and their parents.

Eotaxin, but not IL-8, is increased in upper and lower airways of allergic rhinitis subjects after nasal allergen challenge.

The aim of this study was to assess the impact of a single nasal allergen challenge (NAC) on levels of eotaxin and IL-8 and the inflammatory cells in upper and lower airways of allergic rhinitis (AR) patients. Twenty-four AR patients and 12 control subjects entered a sequential nasal placebo challenge and NAC study, out of the pollen season. Nasal lavage fluid (NLF) was obtained at baseline, 15 minutes, and 1, 5, and 24 hours postchallenge. Before and 24 hours after placebo/allergen challenge induced sputum was performed. NLF and induced sputum were evaluated for total cell count (TCC) and differential cell count and analyzed for concentrations of eotaxin and IL-8 using ELISA method. NAC in AR subjects was associated with significantly increased sputum (p = 0.008) and NLF (p < 0.001) eotaxin levels. Post-NAC IL-8 levels were significantly increased in NLF (p < 00001) but not in sputum (p = 0.080) of AR subjects. Increased eotaxin levels in NLF positively correlated with the increased TCC and eosinophils. Positive correlations were also found between NLF increased eotaxin level and sputum TCC, eosinophils, and macrophages. NAC is associated with the increased levels of eotaxin in lower airways of AR subjects. Allergen-induced secretion of eotaxin in nasal mucosa of AR subjects is involved in determining the cellular character of both upper and lower airway inflammation.

Decreased percentage of CD4+Foxp3+TGF-β+ and increased percentage of CD4+IL-17+ cells in bronchoalveolar lavage of asthmatics

BackgroundAsthma is a chronic inflammatory disorder of the airways with the proven role of Th2 cells in its pathogenesis. The role and characteristic of different subsets of CD4+ cells is much less known.AimThe aim of the study was to analyze the incidence of different subsets of CD4+ T cells, in particular different subsets of CD4+ cells with the co-expression of different cytokines.MethodsTwenty five stable asthmatic and twelve age-matched control subjects were recruited to the study. Bronchoscopy and bronchoalveolar lavage (BAL) were performed in all study subjects. CD4+ T cells were isolated from BAL fluid by positive magnetic selection. After stimulation simultaneous expression of TGF-β, FoxP3, CD25, IFN-γ, IL-4, TNF-α (set 1); IL-10, FoxP3, CD25, IFN-γ, IL-4, MIP-1β (set 2); IL-17A, IL-8, IFN-γ, IL-4, MIP-1β (set 3) were measured by flow cytometry.ResultsThe percentage of CD4+ cells co-expressing Foxp3 and TGF-β (CD4+Foxp3+TGF-β+ cells) was significantly lower (P = 0.03), whereas the percentage of CD4+IL-17+ cells (P = 0.008), CD4+IL-17+ IFN-γ+ cells (P = 0.047) and CD4+IL-4+ cells (P = 0.01) were significantly increased in asthmatics compared with that seen in healthy subjects. A significantly higher percentage of CD4+Foxp3+ cells from asthma patients expressed IFN-γ (P = 0.01), IL-4 (P = 0.004) and CD25 (P = 0.04), whereas the percentage of CD4+IL-10+ cells expressing Foxp3 was significantly decreased in asthmatics (P = 0.03). FEV1% predicted correlated negatively with the percentage of CD4+IL-17+ cells (r = -0.33; P = 0.046) and positively with CD4+Foxp3+TGF-β+ cells (r = 0.43; P = 0.01).ConclusionsOur results suggest that in the airways of chronic asthma patients there is an imbalance between increased numbers of CD4+IL-17+ cells and Th2 cells and decreased number of CD4+Foxp3+TGF-β+.

The rheological properties of blood and the risk of cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS)

Obstructive sleep apnea (OSA) is an important public health concern, which affects around 2-4% of the population. Left untreated, it causes a decrease not only in quality of life, but also of life expectancy. Despite the fact that knowledge about the mechanisms of development of cardiovascular disease in patients with OSA is still incomplete, observations confirm a relationship between sleep disordered breathing and the rheological properties of blood. One possible consequence of an increased incidence of cardiovascular disease may be a rise in mortality in OSA patients. Continuously improved research methods are allowing for an increasingly more accurate understanding of the significance of observed changes.

The use of iloprost in the treatment of ‘out of proportion’ pulmonary hypertension in chronic obstructive pulmonary disease

Case Pulmonary hypertension secondary to respiratory disease most often occurs as a complication of chronic obstructive pulmonary disease, which currently constitutes one of the leading causes of death. Some patients with hypoxaemia reveal “out of proportion” pulmonary hypertension with inappropriate increase of pulmonary artery pressure. Iloprost, analogue of prostacyclin, dilates systemic vessels and pulmonary vessels in particular if administered by inhalation. It appears to be important, life-saving, complementary therapy. However, there is no evidence for its routine use in out of proportion arterial pulmonary hypertension. This case study presents a 44-year old man with chronic obstructive pulmonary disease and “out of proportion” pulmonary hypertension. We present the results of his treatment with iloprost. Conclusion In a patient with “out of proportion” pulmonary hypertension due to chronic obstructive pulmonary disease, inhaled iloprost led to improvement in clinical status and echocardiographic parameters, including a reduction of right ventricular systolic pressure.

Selected growth factors and diffusing capacity of the lung for carbon monoxide in patients with systemic lupus erythematosus

The purpose of the study was to evaluate serum concentrations of selected growth factors and the diffusing capacity of the lung for carbon monoxide (DLCO) in 21 females treated for systemic lupus erythematosus. The control group consisted of 24 healthy women. Based on the high-resolution computed tomography (HRCT), patients were allocated to a subgroup of 11 subjects (HRCT-negative) and a subgroup of 10 with pulmonary abnormalities (HRCT-positive). In HRCT-negative patients a significantly higher level of TNF-α as compared with the control was observed and positive correlation between TNF-α and bFGF was revealed in this subgroup and in the total group of patients. DLCO was below the predicted value in 13 patients. No correlations between DLCO and growth factors concentrations were observed. DLCO reduction in asymptomatic, with respect to the respiratory system, SLE patients suggests a need for long-term monitoring of this parameter. The role of TNF-α in these patients requires further investigations.

Novel method of noninvasive ventilation supported therapeutic lavage in pulmonary alveolar proteinosis proves to relieve dyspnea, normalize pulmonary function test results and recover exercise capacity: a short communication

Whole lung lavage (WLL) under general anesthesia with a double-lumen endobronchial intubation has remained standard treatment option for pulmonary alveolar proteinosis (PAP) for over fifty years now. To the best of our knowledge, this is the first description of noninvasive ventilation (NIV) as an innovative alternative, which enables safe and effective treatment. NIV support enabled cost-effective lavage of the most affected segments and resulted in restoration and long-term maintenance of exercise capacity and diffusion, without WLL related hypoxaemia, volume overload, intubation, or mechanical ventilation related complications. The study presents all details of performed procedure, including anesthesia, NIV technique and bronchoscopy, therefore this may be easily implemented into clinical practice at other centers conducting PAP treatment. We assume that presented technique of therapeutic lung lavage (TLL) with NIV support may be considered a novel PAP treatment method, however, target population who will benefit the most from such therapy modification must be assessed in large scale prospective trials.

Bronchial hyperreactivity in perimenstrual asthma is associated with increased Th-2 response in lower airways

BACKGROUND Perimenstrual asthma (PMA) is a commonly observed, usually difficult-to-treat asthma phenotype. The mechanisms underlying this phenomenon remain unexplained. The aim of the study was to assess the degree of airway hyperresponsiveness and its relationship to proinflammatory cytokines concentration in lower airways of PMA compared to non-PMA patients. METHODS Premenopausal women with regular menstrual cycles diagnosed as: PMA (n=12), non-PMA asthmatics (n=9), and healthy controls (n=10) were prospectively followed for 10 weeks over two consecutive menstrual cycles. The bronchial responsiveness (BR) test to methacholine was performed in each subject prior to the study. The serum for total immunoglobulin E (IgE) concentrations was taken and sputum was induced in the 26th day of each of the two cycles. Sputum concentration of eotaxin, IL-4 and IL-10 were measured by ELISA. RESULTS Levels of BR to metacholine as well, as total blood IgE concentrations in PMA subjects were significantly higher than in non-PMA asthmatics and healthy controls (P=0.001, P=0.022 respectively) and correlated with each other (P=0.030; r =-0.65). Sputum eotaxin and IL-4 concentrations in luteal phase were increased in PMA patients when compared with non-PMA asthmatics (P=0.016; P=0.041, respectively) and healthy subjects (P<0.001 both cytokines). No differences for the sputum levels of IL-10 among studied groups were seen. CONCLUSIONS BR level in perimenstrual asthma is higher than in non-PMA asthmatics and correlates with increased total IgE serum concentration. The increased level of BR in PMA patients is associated with a shift in the type-1/type-2 cytokine balance toward a type-2 response.