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BACKGROUND: Long-term oral corticosteroid (OCS) therapy and related adverse events are associated with a significant burden on patients and healthcare resources. METHODS: This subgroup analysis of a randomized, open-label, parallel-group study evaluated the OCS-sparing effect of omalizumab (OMA) added to optimized asthma therapy (OAT), compared with OAT alone. Patients (12-75 years) with severe allergic asthma, uncontrolled despite GINA 2004 Step 4 therapy, received OMA or OAT for 32 weeks. The change from baseline in OCS use by Week 32 in patients requiring maintenance OCS at baseline was assessed in terms of percent OCS dose change and numbers of patients with reduced/stopped or maintained/increased OCS. RESULTS: Eighty-two patients were receiving maintenance OCS at baseline (OMA/OAT n = 59, OAT n = 23). Change from baseline in mean maintenance OCS dose at Week 32 was significantly greater in the OMA/OAT group compared with the OAT group (-45% vs. + 18.3%, p = 0.002). In the OMA/OAT group, 37 patients (62.7%) reduced/stopped OCS use at Week 32, compared with seven patients (30.4%) receiving OAT (p = 0.013). Improvements in other efficacy outcomes were seen at Week 32 in the OMA/OAT group, irrespective of OCS use. An investigator global evaluation of treatment effectiveness at Week 16 was an effective predictor of persistent treatment response at 32 weeks for the majority of OMA/OAT patients (93%), also irrespective of OCS use. CONCLUSION: In this open-label study of patients with severe allergic asthma, OMA/OAT therapy reduced maintenance OCS use, compared with OAT alone. Improvements in efficacy measures were observed in the OMA/OAT group, irrespective of OCS change. CLINICALTRIALS.GOV IDENTIFIER: NCT00264849. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary artery hypertension and its consequences still constitutes an underestimated clinical problem in asthma patients and its non-invasive early detection may influence proper treatment., Aim: To non-invasively examine the pulmonary artery flow parameters and right ventricular function in patients with asthma of various severity., Material and Methods: The analysis of parameters of echocardiography and first-pass and gated radionuclide angiography, and baseline examination in 31 patients with bronchial asthma and 16 healthy controls., Results: Patients with severe asthma had higher mean pulmonary artery pressure (MPAP) compared to the healthy controls. The subgroup analysis of patients who suffered from asthma in their childhood showed that individuals with severe asthma were characterized by significantly higher MPAP than those with the mild/moderate condition (19.16 ±7.51 mm Hg vs. 5.0 ±1.15 mm Hg, p = 0.025). Gated, but not first-pass, radionuclide angiography revealed that individuals with severe asthma were characterized by a lower right ventricular ejection fraction (RVEF). Further analysis of the subgroup of patients in whom the initial manifestation of dyspnoea occurred no earlier than 6 years prior to the study showed that the RVEF of individuals with severe asthma was significantly lower compared to those with mild/moderate asthma (39.8 ±4.79% vs. 51.4 ±8.65%, p = 0.019)., Conclusions: The pulmonary artery pressure in patients with severe asthma is significantly higher than in healthy individuals; in contrast, these two groups did not differ significantly in terms of the right ventricular echocardiographic characteristics. Gated radionuclide angiography, but not the first-pass technique, allowed for the detection of subtle right ventricular ejection fraction changes in asthma patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Purpose: Recognition of individual allergens by IgE is crucial for triggering symptoms in allergic rhinitis (AR) or asthmatic (AA) patients. House dust mite (HDM) allergy is frequent around the world, the sensitization profile to individual HDM allergens varies in individual HDM-allergic patients (APs). The aim of this study was to evaluate the pattern of IgE sensitization to three major Dermatophagoides pteronyssinus (Dp) allergens among patients from North Eastern Poland suffering from HDM-AR and/or AA., Patients and Methods: The study was performed on 323 HDM-AR and/or AA patients and 106 controls (CG) including 30 healthy non-atopic subjects, 32 AR patients not sensitized to Dp and 44 non-atopic asthmatics. IgE levels to natural (n)Der p 1, nDer p 2, recombinant (r)Der p 2.0101 and rDer p 23 allergens were measured by ELISA., Results: The majority of HDM-APs were sensitized to nDer p 1 (72.1%), nDer p 2 (81.7%), rDer p 2.0101 (78.3%) and rDer p 23 (70.9%). The frequency of positive results to individual allergens depended on clinical manifestations and the level of IgE to the whole Dp extract. In HDM-AA patients, reactivity to nDer p 1 and rDer p 23 was detected more frequently than in HDM-AR patients. The whole Dp extract completely inhibited IgE binding to nDer p 1 and nDer p 2 but only partially to rDer p 23., Conclusions: HDM-APs from North-Eastern Poland display sensitization profile to major allergens which is similarly observed in western Europe. HDM-based diagnostic and therapeutic products should include all major allergens., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The presence of immunoglobulin E (IgE), which cross-reacts with allergen components, such as profilins, polcalcins, and cross-reacting carbohydrate determinants (CCD), creates a problem when selecting patients for allergen immunotherapy by using conventional methods. The aim of this study was to evaluate the prevalence of sensitization to profilins, polcalcins, and CCDs in patients with seasonal pollen allergic rhinitis. Methods: The study was performed on a group of 112 patients with seasonal pollen allergic rhinitis, ages 14 to 55 years, with sensitization to at least one seasonal allergen (IgE > 0.7 kUA/L). The presence of IgE sensitization to recombinant (r) Bet v 2, rPhl p 12, rBet v 4, rPhl p 7, and CCDs, in addition to rBet v 1, rPhl p 1, rPhl p 5, was evaluated by using a multiparameter immunoblot. Results: Among the studied patients, 64.3, 80.4, and 41.1% were sensitized to birch, timothy grass, and mugwort pollen, respectively. Sensitization to profilins rBet v 2/Phl p 12 was demonstrated in 28.6%, to polcalcins Bet v 4/Phl p 7 in 8.9%, and to CCDs in 25%. In 29.3%, serum IgE reactivity to any of the cross-reactive components could be demonstrated. Serum IgE reactivity to rBet v 2 was always accompanied by IgE reactivity to rPhl p 12, and IgE reactivity to rBet v 4 was always accompanied by IgE reactivity to rPhl p 7. Among the patients with pollinosis co-sensitized to at least two allergen sources according to extract-based diagnosis, possible false-positive results due to sensitization to cross-reactive components were detected in 17.9%. Conclusion: Evaluation of sensitization to cross-reacting components may be useful in evaluation of patients with pollen allergy who are being assessed for allergen immunotherapy to optimize the constitution of their immunotherapy vaccines.

Background: A high strength of beclomethasone/formoterol fumarate (BDP/FF) in a pressurised metered dose inhaler (pMDI), which contains extrafine BDP (200 μg/actuation) and FF (6 μg/actuation) has been developed to treat those asthmatics who are not adequately controlled on previous treatments., Methods: A 12-week, randomized, double-blind, parallel group study was performed to compare the efficacy and safety of pMDI BDP/FF 200/6 (two actuations bid) with BDP 100 μg (four actuation bid) in a population of 376 randomized adult asthmatics not adequately controlled with high dose of inhaled corticosteroids (ICS) or medium dose of ICS plus long acting β 2 agonists (LABA)., Results: The primary endpoint [change from baseline over the entire treatment period in average pre-dose morning peak expiratory flow (PEF)] demonstrated the superiority of BDP/FF over BDP monotherapy, with an adjusted mean difference of 19 L/min, which is above the minimal important clinical difference reported for this parameter. Overall, BDP/FF and BDP showed a similar improvement of symptom-based parameters and of the use of rescue medication after 3-month treatment. The safety profile of the two drugs was comparable, although BDP monotherapy, but not BDP/FF, slightly reduced the levels of serum cortisol., Conclusions: The study proved that pMDI BDP/FF 200/6 μg was superior to BDP alone in improving lung function with comparable safety profiles. Therefore it may be considered as an effective treatment for adults with asthma not adequately controlled with high dose of ICS monotherapy or medium dose of ICS/LABA combinations., Trial Registration: ClinicalTrials.gov: NCT01577082 , date 06/04/2012.

Unlabelled: This multicentre, double-blind, randomised, placebo-controlled, crossover study aimed to determine the dose-response of the long-acting muscarinic antagonist (LAMA) glycopyrronium bromide (GB) when added to beclometasone dipropionate plus formoterol fumarate (BDP/FF) in patients with COPD. Patients received extrafine GB 12.5, 25 or 50 μg twice daily (BID) or placebo for 7 days via pressurised metered dose inhaler (pMDI), and extrafine BDP/FF via pMDI throughout the study. The primary objective was to demonstrate superiority of GB plus BDP/FF versus BDP/FF in terms of FEV1 area under the curve from 0 to 12 h (AUC0-12h) on Day 7. Secondary endpoints included: FEV1 AUC0-12h on Day 1; peak FEV1 and FVC on Days 1 and 7; and trough (12 h post-dose) FEV1, FVC and inspiratory capacity (IC) on Days 1 and 7. Of 178 patients randomised (mean age 62.7 years, post-bronchodilator FEV1 48.9%), 172 (96.6%) completed. Mean FEV1 AUC0-12h on Day 7 was significantly higher (p < 0.001) for all GB doses plus BDP/FF compared to BDP/FF alone, with the difference for the 25 and 50 μg BID doses being clinically relevant (i.e., ≥100 mL). The results for the other spirometry endpoints were consistent with the primary endpoint. Adverse events were reported in 7.4, 5.7 and 8.0% of patients receiving GB 12.5, 25 and 50 μg BID, respectively, versus 11.0% of patients receiving BDP/FF alone. This study confirms the value of adding GB to BDP/FF to improve lung function in COPD patients. The dose of extrafine GB 25 μg BID was associated with the best efficacy/safety profile., Trial Registered at: ClinicalTrials.gov., Registration Number: NCT01476813., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: There are many potential factors that can modulate bronchial reactivity, including exposure to allergens, viral infections, and medications. The aim of this study was to analyze the effect of grass pollination intensity on the bronchial reactivity in seasonal allergic rhinitis (SAR) patients subjected to subcutaneous allergenic immunotherapy (SCIT)., Material and Methods: This study, performed between 2005 and 2008, included 41 patients with confirmed sensitivity to grass pollens and predominating symptoms of SAR, randomly assigned to desensitization by pre-seasonal or maintenance SCIT. Bronchial provocation challenge with histamine was performed before the onset of immunotherapy, and repeated three times after each pollen season covered by this study. Bronchial reactivity was analyzed with regard to grass pollination intensity in 2005-2008 (air concentration of grass pollen grains, seasonal number of days when air concentration of grass pollen reached at least 20 or 50 grains per 1 m(3))., Results: After 3 years of SCIT, a significant decrease in bronchial responsiveness was observed in the analyzed group as confirmed by an increase in PC20 FEV1 histamine values (p = 0.001). An inverse tendency was observed after 2 years of SCIT, however. This second year of SCIT corresponded to the 2007 season, when a significantly higher number of days with at least 50 grains of pollen per 1 m(3) of air was recorded., Conclusions: FLUCTUATIONS IN POLLINATION INTENSITY OBSERVED DURING CONSECUTIVE YEARS OF IMMUNOTHERAPY CAN INFLUENCE BRONCHIAL REACTIVITY IN PATIENTS SUBJECTED TO SCIT (ISRCTN REGISTER: ISRCTN 86562422).

Background: According to international treatment guidelines, inhaled rapid-acting β2 agonists should be used for the control of symptoms in patients with asthma. We compared the efficacy and safety of an extrafine combination inhaler containing a corticosteroid (beclometasone) plus a rapid-onset, long-acting β2 agonist (formoterol) with a short-acting β2 agonist (salbutamol) as reliever strategies in patients taking beclometasone-formoterol combination as maintenance treatment., Methods: In a double-blind trial undertaken in 183 centres in 14 European countries over 48 weeks, patients (aged ≥18 years) with asthma that was not fully controlled, with a forced expiratory volume in 1 s (FEV1) of at least 60% predicted, had a 2-week run in. During this period, patients were treated with a combination of beclometasone 100 μg and formoterol 6 μg per one inhalation twice daily plus salbutamol 100 μg as required delivered by use of a pressurised metered-dose inhaler. They were then randomly assigned in a 1:1 ratio with a computer-generated randomisation list to receive beclometasone 100 μg plus formoterol 6 μg or salbutamol 100 μg as reliever in addition to maintenance with beclometasone 100 μg plus formoterol 6 μg twice daily. Primary outcome was the time to first severe exacerbation (admission to hospital or visit to emergency department, or use of systemic steroids for ≥3 consecutive days). Secondary outcomes were number of severe exacerbations (events per 100 patients per year), time to and number of mild exacerbations, additional exacerbation variables, lung function, symptom scores, and asthma control. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00861926., Findings: 1714 patients were randomly assigned to the as-needed beclometasone-formoterol (n=857) and as-needed salbutamol groups (n=857), and 1701 were analysed (852 and 849, respectively). 326 severe exacerbations were reported by 251 patients during the study, and 99 versus 152 patients had at least one exacerbation during the 48 weeks, respectively. Compared with beclometasone-formoterol plus salbutamol as needed, beclometasone-formoterol for both maintenance and reliever treatment significantly increased the time to first exacerbation (209 days vs 134 days) by 75 days, with a 36% reduction in risk (hazard ratio 0·64 [95% CI 0·49 to 0·82]; p=0·0005), and the estimated probability was 12% and 18%, respectively (p=0·0003). The number of days with mild asthma exacerbations was also lower with as-needed beclometasone-formoterol than with as-needed salbutamol (56·04 days per patient per year vs 65·11 days per patient per year; 0·86 [0·76 to 0·98]; p=0·021). From the run-in period to week 48, both treatments improved symptoms (mean change -1·59 [-1·94 to -1·25] in the as-needed beclometasone-formoterol group vs -1·44 [-1·78 to -1·10] in the as-needed salbutamol group, difference -0·15 [-0·60 to 0·30]; p=0·507), percentage of asthma control days (9·5% [7·3 to 11·8] vs 10·9% [8·7 to 13·1], respectively, -1·4 [-4·3 to 1·6]; p=0·359), use of reliever (-0·29 [-0·38 to -0·20] vs -0·27 [-0·36 to -0·19], respectively, -0·02 [-0·13 to 0·10]; p=0·794), and lung function (FEV1, 0·090 [0·060 to 0·120] vs 0·090 [0·060-0·120], respectively, 0·001 [-0·040 to 0·040]; p=0·969), and were well tolerated (patients with serious adverse events, 32 [4%] and 41 [5%], respectively)., Interpretation: Our results lend support to the use of the combination of a single inhaled corticosteroid plus a rapid-onset, long-acting β2 agonist for maintenance and relief in patients with moderate to severe asthma and provide encouraging data for the formulation of beclometasone-formoterol for this use., Funding: Chiesi Farmaceutici., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to compare the usefulness of mannitol provocation test to that of classical histamine challenge in children with PC(20)FEV(1) histamine lower than 4 mg/ml., Methods: Twenty-two adolescent patients (mean age of 15.4 ± 4.1 years) with established asthma (PC(20)FEV(1) histamine below 4 mg/ml) were included in this study. Bronchial challenge with mannitol was performed 1-2 days after the test with histamine., Results: The fraction of positive results of mannitol test was markedly lower when compared with the histamine challenge (72.7% vs. 100%, p = .015). The test was discontinued in one case due to severe coughing after inhalation of 315 mg of mannitol. Coughing during inhalation of dry mannitol powder occurred in most patients, although drinking water after subsequent doses alleviated this symptom in nearly all of them. Of note, triboelectrification of the inhaler and capsules was observed during the administration of consecutive mannitol doses, markedly hindering the delivery of this provoking agent. The relative decrease in FEV(1) resulting from bronchial provocation was significantly lower following mannitol delivery when compared with the histamine test (70.3% vs. 81.6% of resting value, p < .001). Significant correlation was not observed between the values of PC(20)FEV(1) histamine and PD(15)FEV(1) mannitol levels., Conclusions: Bronchial challenge with mannitol can be used as a screening test in everyday practice, but one cannot exclude bronchial hyperresponsiveness based on its negative results. Moreover, its usefulness is limited by the influence of static on the delivery of sequential mannitol doses and coughing which can be often associated with mannitol inhalation.

Background: Concentration of nitric oxide in exhaled air (FeNO) was revealed to decrease as a result of immunotherapy. However, individuals who are exposed to environmental allergens are characterized by elevated values of FeNO. The aim of this study was to analyze the effects of subcutaneous immunotherapy (SCIT) on the dynamics of FeNO determined during consecutive pollination seasons., Methods: This study, performed between 2005 and 2008, included 41 patients with confirmed sensitivity to grass pollens and predominating symptoms of seasonal allergic rhinitis, randomly assigned to desensitization by preseasonal or maintenance SCIT. FeNO was measured prior to and during each pollen season (November-January and May-July, respectively). The results were conferred to data on grass pollination intensity in 2006-2008 (air concentration of grass pollen grains, seasonal number of days when air concentration of grass pollen reached at least 50 grains per 1 m(3))., Results: Median content of FeNO in exhaled air was significantly higher in 2007 compared to 2006 and 2008 pollen seasons. During 2007 and 2008 pollen seasons, significant increase in FeNO was observed compared to the respective preseasonal values. Median number of days with air concentration of grass pollen ≥ 50 grains per 1 m(3) of air during 4 weeks preceding seasonal FeNO measurement was significantly higher in 2007, corresponding to higher FeNO value recorded during this pollen season. However, no significant correlation was observed between seasonal number of days with ≥ 50 grass pollen grains per 1 m(3) of air and FeNO in exhaled air (r=0.09, p=0.362)., Conclusions: Most seasonal allergic rhinitis patients show physiological levels of FeNO prior to the pollen seasons and a marked increase in this parameter, probably proportional to pollination intensity, is observed within the seasons. ISRCTN Registry: ISRCTN86562422.

Objective: Carcinoids are low-grade, slow growing malignant tumors in the bronchi usually producing symptoms secondary to bronchial obstruction. We describe a case of 25-year-old woman who was initially diagnosed with asthma., Method: Case report., Results: Because of exacerbation and unresponsiveness to proper asthma treatment she was referred to spirometry, which showed low values of forced expiratory volume in 1 second. The shape of inspiratory limb of flow volume curve suggested an obstruction in the main bronchus or in the trachea. Further bronchoscopy revealed a tumor of the right main bronchus with characteristic histological features for carcinoid., Conclusions: Both the inspiratory curve and the expiratory part of the flow-volume loop should be evaluated in patients being evaluated for asthma. If there are changes in the shape of the inspiratory limb suggesting an obstruction, CT and/or bronchoscopy should be considered.

Background: Changes in fractional exhaled nitric oxide (FeNO) occurring after bronchial allergen challenges (BAC) are still not understood, neither are any possible associations between FeNO and forced expiratory volume in 1 sec (FEV(1)). The aim of the study was to compare the fluctuations of FeNO and FEV(1), which occur within 72 h of BAC in children sensitive to grass pollen., Methods: Seventy-four children were divided into two groups based on their medical histories and the results of skin prick tests with 10 common allergens. Individuals in whom the test yielded a positive result to at least grass pollen (Group A, n = 57), and those with negative test results against all of the allergens applied (Group B, n = 17) were subjected to BAC. FeNO was measured at a baseline and at 1, 8, 21, and 72 h after the last dose of the allergen inhalation, whereas FEV(1) was measured at a baseline, hourly for 8 h after the challenge and at 21 and 72 h thereafter., Results: Baseline FeNO in sensitive subjects (Group A) was significantly higher than in controls of Group B. In all grass pollen-sensitive subjects, even those that were free of a bronchial response, FeNO was markedly elevated compared to its baseline values, starting from the eighth hour onward, and still increased 72 h post-BAC, whereas FEV(1) returned to a baseline at the 72nd h post-BAC. The highest increase in FeNO was registered in individuals with a dual asthmatic response., Conclusions: An increase in FeNO in sensitive subjects starts a few hours later than the decrease in FEV(1). Consequently, measurements of FeNO seem to be useful in long-term monitoring of the allergic reaction triggered by a specific allergen.

Unlabelled: Birch pollens are known as seasonal asthma precipitants. Our earlier studies evidenced a very high frequency of positive results bronchial allergen challenges in pollinosis patients sensitive to grass pollen. The aim of the study was to evaluate how often the bronchial challenge with birch pollen allergen causes bronchoconstriction., Material and Methods: Studies were performed outside of pollen season on 30 patients sensitive to birch pollen allergen. Before the allergen challenges bronchial provocation tests with methacholine were performed in all subjects., Results: About 13% of examined group had bronchial hyperreactivity (PC20FEV1Mch < 8 mg/ml) and 50% demonstrated bronchoconstriction after birch pollen allergen inhalation., Conclusions: About 13 percent of patients sensitive to birch pollen demonstrated nonspecific hyperrectivity out of pollen season. Bronchial birch allergen challenge tests are positive in about half of birch sensitive patients with pollinosis.

Unlabelled: Bronchial hyperreactivity, a inseparable feature of asthma in polish asthmatics is seldom evaluated. Its depends on at least two causes i.e. a lack of methacholine registration for BPT and an opinion, that challenge test can be harmful or dangerous for patients. That situation could correct wider prevalence of bronchial provocation test with hypertonic saline. To perform the test are needed: spirometer, ultrasonic nebuliser and hypertonic saline. The aim of the study was to compare sensitivity and specifity of both tests with methacholine and hypertonic saline., Material and Methods: Studies were carried out on a group of 79 subjects, where was 59 asthmatics and 20 healthy subjects (control group). Sensitivity and specifity of both tests were evaluated for a few different thresholds considered as a positive result. Usually a 20% decrease of FEV1 from baseline was considered as positive test result. Three different thresholds were considered for methacholine test i.e. PC20FEV1 = 8,0 or 16,0 or 32,0 mg/ml. Relative to BPT with hypertonic saline maximal inhalation time was constant, i.e. 930s, but different decreases in FEV1 (15% or 20% from baseline) were needed., Results: The most comparable sensitivity and specifity of the both tests were following, for methacholine threshold = PC20FEV1 = 16 mg/ ml, and for 4,5% NaCl PT15FEV1 = 930s., Conclusion: Although BPT with hypertonic saline is less sensitive than methacholine challenge, it seems to be a good tool to evaluate of bronchial hyperreactivity and should be more often applied.

Unlabelled: Pollinosis is the most common disease in the world in people touched by atopy. The aim of the study was to evaluate seasonal changes in serum levels of EDN, IL-18, and IFN-gamma., Material and Methods: Studies were carried out on a group of 30 patients suffering from pollinosis, sensitive to pollen of Ryegrass engl. Twenty healthy subject were considered as a control group. Blood samples were collected in June and December. The concentrations of above mentioned substances were evaluated using ELISA method., Result and Conclusion: In pollen season the significant increase in concentration of EDN, and IL-18, and no changes in serum concentration of IFN-gamma were found.

The Aim of the Study: To evaluate seasonal changes in bronchial hyperreactivity (BHR) in patients suffering from pollinosis, sensitive to Ryegrass engl., Material and Methods: The studies were carried out on 26 patients and 20 healthy subjects. All the patients had a history of seasonal allergic rhinitis. The following measurements were performed outside and during the pollen season: bronchial provocation test (BPT) with metacholine and 4.5% NaCl, serum concentration of specific and total IgE., Results: Outside the pollen season additionally the BPT with Ryegrass engl. allergen was performed and 88% of the pollinosis patients had positive result of the test. After 4.5% NaCl bronchial challenge positive results had 2 out of 26 patients outside the season, and 3 during the season. Bronchial hyperreactivity to metacholine (PC20 < 8 mg/ml) were observed in 4/26 (15.4%) persons outside the season and in 7 (26.9) during the season. The healthy subjects had no bronchoconstriction neither after metacholine or 4.5% NaCl. During the pollen season the increase in serum concentration of tIgE and sIgE was observed only in pollinosis patient., Conclusions: There was not found a correlation between BHR to the allergen and serum total IgE nor specific IgE concentration.

The authors present a case of an 18-year-old woman, were referred to an allergologist because of a suspicion of bronchial asthma. She had complained of respiratory symptoms: chronic bronchitis for three years, cough and dyspnoea. Auscultation revealed wheezies and rales. Spirometry showed severe airway obstruction. Because of negative result of a reversibility test, ex iuvantibus treatment with prednisone was used but no results were obtained. The next step of diagnostic procedure was computed tomography which revealed the trachea compression by the dilated oesophagus. Finally she was found by us to have esophageal achalasia. Pharmacological treatment with nifedipine did not give an improvement. After operation the asthmatic symptoms disappeared and marked improvement was found in the flow-volume curve and in the chest radiogram. The demonstrated case proves that esophageal achalasia should be considered as one of the differential diagnoses of pathological respiratory symptoms suggesting asthma difficult to treat.

Scientific studies of the material obtained during bronchial biopsy, bronchoalveolar lavage and sputum induction altered the view on the pathogenesis of asthma and COPD. In the result, both bronchial diseases are considered inflammatory. Eosinophils play the main role in the pathogenesis of asthma, whereas in COPD the most significant are neutrophils. Bronchial biopsy and bronchoalveolar lavage have been applied mainly in scientific studies, while sputum induction as a non-invasive method can be useful in everyday practice too. Increased level of eosinophils in sputum allows to forecast the efficiency of glucocorticosteroids in the therapy of asthma and COPD.

Objective: The leukotrienes are a family of arachidonic acid-derived lipid mediators with proinflammatory and profibrotic properties. The aim of this study was to analyze the role of leukotriene B(4) (LTB(4)) and LTE(4) in the pathogenesis of scleroderma lung disease (SLD)., Methods: Nineteen systemic sclerosis (SSc) patients with SLD, 11 SSc patients without SLD, and 10 healthy controls were studied. Bronchoalveolar lavage (BAL) fluid was obtained during routine bronchoscopy of the right middle lobe in all study subjects. Levels of LTB(4) and LTE(4) were measured using enzyme immunoassay kits., Results: Levels of LTB(4) and LTE(4) were significantly higher in SSc patients with SLD (251 +/- 170 pg/ml and 479 +/- 301 pg/ml, respectively), than those in patients without SLD (114 +/- 86 and 159 +/- 149 pg/ml) and those in normal controls (86 +/- 49 and 110 +/- 67 pg/ml). In the total group of patients with SSc, levels of both leukotrienes correlated positively with the total number of cells in the BAL fluid and correlated negatively with the forced vital capacity. After intravenous pulse therapy with cyclophosphamide in 6 patients, there was a significant reduction in the concentration of LTB(4) (from 380 +/- 196 pg/ml to 155 +/- 123 pg/ml) but no significant difference in the levels of LTE(4) (from 697 +/- 325 pg/ml to 418 +/- 140 pg/ml)., Conclusion: Our findings show that LTB(4) and LTE(4) levels are elevated in SSc patients with SLD and correlate with parameters of inflammation in the lungs. These results indicate that leukotrienes may contribute to the pathogenesis of SLD and may represent a new therapeutic target.

CD69 molecule is the earliest antigen of T lymphocytes activation. We have studied the ex-pression of CD69 on LPS-stimulated T cells in nonatopic bronchial asthma. We have found that CD69 expression on freshly isolated peripheral blood T cells in nonatopic asthma patients was increased compare to control group (4.74 +/- 1.55/3.05 +/- 1.31) and the difference was statistically significant (p < 0.01). Monocytes added to nonstimulated T cell cultures increased 3-4 times the expression of CD69 and about 10-times in LPS-stimulated T lymphocytes.

We have studied the effect of CD80 (B7.1) and CD86 (B7.2) costimulatory molecules inactivation on IL-4 and IFN-gamma production by T lymphocytes. T cells were received from nonatopic asthmatic and healthy subjects. We have added anti-CD80 or anti-CD86 monoclonal antibodies to the monocyte/lymphocyte (1:5) cultures. In nonatopic asthma patients compare to control group inactivation of CD80 significantly reduced IFN-gamma production by T lymphocytes (2172/2368 pg/ml; p < 0.02). Blockade of CD86 decreased IFN-gamma production non-significantly (2858/3317 pg/ml; p < 0.3). In both studied groups anti-CD80 antibodies did not diminish T lymphocyte production of IL-4 (control: 630/725 pg/ml; nonatopic asthma: 718/742 pg/ml). Anti-CD86 antibodies reduced the IL-4 concentration in culture supernatants (630/523 pg/ml; 718/659 pg/ml), but the changes were nonsignificant.

Inhalation of hypertonic saline aerosol is a noninvasive method of obtaining sputum for examination of inflammatory processes in the airways. The aim of our investigation was to evaluate the effect of the bronchial provocation test with Dermatophagoides pteronyssinus on both total and differential cell counts in the sputum of allergic asthma patients. The studies were carried out on 20 mild or moderate allergic asthmatics. In each case the studies were performed on three consecutive days. Sputum was induced on the first day of the study, the next day the bronchial provocation test with the allergen was performed and on the last day the sputum induction was repeated again. Twenty-four hours after the allergen challenge an increase in the total cell count and in eosinophils and a decrease in the percentage of macrophages were found in the induced sputum. The above changes were more marked in the patients demonstrating the dual asthmatic reaction after allergen challenge.

The value of Dpt allergen extract, produced by Allergopharma J.G., for performance of the bronchial provocation test in asthmatics was evaluated. The studies were carried out in 40 asthmatics with positive skin prick test with Dpt. Bronchial provocation test was performed according to Ryan's method. After an allergen inhalation, an early asthmatic reaction (EAR) and late asthmatic reaction (LAR) may appear. The following results were observed: a dual asthmatic reaction (EAR and LAR)--in 19 persons, the EAR--only in 9 patients, and the LAR--only in 1 patient. The negative result of the provocation were found in 11 patients. The frequency of particular patterns of the bronchial reactions was similar to those published before by us and other authors, with different allergen extracts. The allergen extract of Dpt from Allergopharma J.G. can be used to bronchial challenge.

Evaluation of differential cell count and biochemical parameters in sputum seems to be a valuable method in asthma studies. The purpose of the paper was to evaluate the effects of sputum induction alone and after fenoterol and salmeterol premedication, on spirometry in asthma patients. The another aim of the study was to observe the correlation between bronchial hyperreactivity and decreases in FEV1 and MEF50 in asthmatics during sputum induction. The studies were carried out on 20 mild to moderate asthma patients (FEV1 baseline 79 +/- 16% of the predicted values) who inhaled an increasing concentration of hypertonic saline (3%, 4% and 5%), using an ultrasonic nebuliser. The forced expiratory volume in one second and MEF50, as the good indicators of bronchial obturation, were evaluated. During the sputum induction significant decreases in FEV1 and MEF50 were observed, which were proportional to the concentration of NaCl. After inhalation of 3% of NaCl the mean of FEV1 was 87.2 +/- 12.7% of the baseline, after 4%--84.3 +/- 16.9% and 5%--77.4 +/- 19.8%. No significant correlation between bronchial hyperreactivity and the induced decreases in FEV1 and MEF50 were found. Fenoterol and salmeterol fully prevented bronchial obturation during sputum induction.

The purpose of the study was to determine whether regular administration of budesonide R decreases inflammation, specific and non-specific bronchial hyperreactivity in allergic asthma patients. The studies were carried out on 16 patients suffering from mild to moderate allergic asthma, sensitive to D. pteronyssinus allergen. After performance of the specific and non-specific bronchial provocation tests, collection of blood samples for an ECP evaluation, the patients were regularly treated with budesonide R, 2 x 320 micrograms for a period of 8 weeks. At the end of the study the BPTs and blood collection were repeated. BPTs with methacholine and D. pteronyssinus were performed according to Ryan's method. After the allergen challenge, early (EAR) and late asthmatic reaction (LAR) were to be observed. After the therapy non-specific BHR to methacholine expressed as PC20FEV1 and specific BHR to allergen (PD20FEV1D. pteronyssinus) and serum ECP concentrations decreased significantly. Although after the treatment with budesonide R, the patients had to inhale much larger amounts of allergen, in order to induce EAR, the number of LAR did not change significantly. After treatment the LAR appeared about 1 hour later and the decrease in FEV1 was less than previously. We conclude that budesonide R decreases the intensity of the inflammation and BHR.

The effect of a single dose of 320 micrograms of budesonide R on specific and non-specific bronchial response was evaluated. The study was carried out on a group of 12 patients suffering from mild allergic asthma, sensitive to Dermatophagoides pteronyssinus (D. pteronyssinus). On the first day the bronchial provocation test (BPT) with metacholine was performed, and the next day the effect of a single dose of the drug studied on bronchial response to metacholine was evaluated. On the third day sBPT with D. pteronyssinus allergen was performed. The allergen challenge could induce an early (EAR) and a late asthmatic reaction (LAR). After the BPT with the allergen, a 42 days' run-out period was required to eliminate the effects of the allergen provocation on the results of the next tests. Before the evaluation of the effect of budesonide on the allergen challenge, the non-specific response to metacholine was checked again. The results indicate that a single dose of budesonide R does not affect non-specific and specific bronchial response.

The purpose of the study was to evaluate the efficacy of salmeterol in asthma therapy. The study was performed on a group of 16 allergic asthma patients sensitive to house dust mite allergens. After a run-in period the patients were treated with salmeterol, 2 x 50 micrograms, for a period of 12 weeks. They noted an intensity of asthma symptoms, morning and evening PEF, beta 2-agonist consumption and adverse in their diary cards. On the visit to the clinic spirometry was performed. During the treatment a significant reduction in the symptom score, PEF variation, beta-agonist consumption and an increase in the value of morning and evening PEF were noted. The above results indicate the great efficacy of salmeterol in asthma therapy.

The effect of a single dose of salmeterol, long-term, regular treatment with salmeterol and a termination of the therapy on specific and non-specific bronchial reactivity were evaluated. The effect of the therapy on serum ECP level was studied too. The studies were carried out in a group of 16 mild asthmatics sensitive to mite allergens. Both types of bronchial challenges were performed according to Ryan's method. Blood samples to evaluate the ECP level were collected before treatment and on the day before the last day of the study. The single dose of 50 micrograms of salmeterol taken 3 hours before bronchial challenge significantly decreased the bronchial response to histamine (the average PC20FEV1 value increased about a four fold after salmeterol) and to the Dpt allergen (PD20FEV1 increased 3.5 fold). No effect of salmeterol on LAR was observed. Bronchial reactivity to histamine was significantly lower in the period of the therapy and did not differ from the baseline 12 hours after stopping the treatment. PD20FEV1 Dpt during the therapy was about 3 fold higher than the baseline but 36 hours after stopping the treatment did not differ from the baseline. Although the patients had inhaled a 3-fold higher dose of allergen to induce EAR, the frequency of LAR did not change. No anti-inflammatory effect of salmeterol was observed.

The efficacy, tolerance and, in addition, the effect of the antiasthmatic drug-Ditec, consisting of low doses disodium cromoglycate (DSCG) and fenoterol on bronchial hyperreactivity (BHR) were evaluated. The studies were carried out on a group of 22 mild asthma patients aged from 10 to 20 years. The patients took DSCG during the first four weeks and then were treated with Ditec, 4 x 2 puffs, for next four weeks. The following parameters were evaluated: symptom score, beta 2-agonist "taken on demand" consumption, spirometry, morning and evening PEF, and possible adverse effects. Decreases in the symptom score, beta 2-agonist consumption (mainly in Ditec period) and increase in PEF during the study were noted. The low doses of DSCG contained in Ditec were as effective as the 80 mg of this drug given previously. No statistically significant decrease in BHR after DSCG treatment was observed. At the end of the Ditec therapy, BHR to histamine markedly diminished. Because the last doses of Ditec were taken 2 hours before the bronchial provocation test with histamine, the increase in tolerance of histamine, mentioned above, was probably only due to the so-called acute effect of beta 2-agonist on BHR. Ditec seems to be a valuable antiasthmatic drug, especially for children and young persons. Unfortunately, our studies did not answer the additional question whether regular treatment with Ditec changes BHR.

The value of the allergen extract, Aquagen SQ-Dpt, for performance of the bronchial provocation test in allergic asthma patients was evaluated. The studies were carried out on 117 patients suffering from allergic mite asthma. Bronchial challenge was performed according to Ryan's method. After an allergen inhalation, an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) may appear. In our studies a dual reaction (EAR and LAR) was observed in 53.8% of the patients, the EAR only in 27.4% and the LAR only in 2 patients. The subjects with the dual response demonstrated a higher sensitivity to the allergen than those with only the EAR. A positive, statistically significant correlation between specific and non-specific bronchial hyperreactivity was found. The frequency of the appearance particular patterns of the bronchial responses was similar to those published by other authors, using different allergen extracts. Aquagen SQ-Dpt can be used to perform of the sBPT.

The effects of two selective H1 receptor blockers, cetirizine and loratadine, in comparison with placebo, on basophil histamine release and the bronchial response to histamine were assessed. The studies were performed in a group of 18 patients with pollinosis and 22 with atopic asthma. Both tests were performed before and after medication. Histamine release from isolated basophils was evaluated by Shore's method using anti-IgE and pollen antigen as stimulants. The bronchial provocation tests were performed by Ryan's method. The results were expressed as PC20FEV1. It was shown that both drugs significantly inhibited basophil histamine release induced by anti-igE or specific allergen. It was also found that these drugs effectively reduced the bronchial response to histamine challenge. These findings confirm the beneficial clinical effect of a new generation of selective H1 blockers in the treatment of IgE-mediated allergic diseases, and also the possible role of these drugs in the therapy of atopic asthma.

Changes in particular spirometry parameters during specific bronchial provocation test (BPT) with an allergen in asthmatics sensitized to house dust mites were evaluated. Studies were carried out on 130 patients. Specific BPT with D. pteronyssinus was performed according to the Ryan's method using a jet De Villbiss 646 nebuliser powered by compressed air and connected to the French Rosenthal dosimeter. The spirometry was measured using Pneumoscreen II (Jaeger - Germany). The provocation was terminated when a value of FEV1 fell at least 20% from baseline and then the spirometry parameters were measured hourly for a period 8 hours. Early and late asthmatic responses were founded. Results were expressed as a percentage of the maximum decrease from the baseline in particular parameters. To the statistical calculations only positive sBPT results founded in 96 patients were selected. The mean values of the decreases during of the EAR were as follow: FEV1 = 30.6 +/- 9.9%, FVC = 18.9 +/- 9.9%, FEV/FVC = 14.6 +/- 9.2%, FEV25-27 = 41.5 +/- 15.7%, PEF = 30.8 +/- 15.7%. The correlation coefficients were between FEV1 and FVC -0.57, FEV1 and FEV1/FVC -0.56, FEV1 and FEF25.75 -0.65, FEV1 and PEF -0.6. The results were statistically significant. Decreases in FEV1 and PEF were very similar each other. The greatest changes were observed in FEF25.75. The curves of the FEV1 and PEF averages observed during LAR were quite close to each other and almost parallel. The usefulness of the both parameters seems to be equal.

The aim of this study was to determine the relation between specific Bronchial Provocation Test (sBPT), the serum specific IgE level (sIgE) and specific basophil histamine release (Dpt HR) in asthma patients, sensitive to Dermatophagoides pteronyssinus (Dpt). The studies were carried out on 30 mild asthma patients with positive case history and strongly positive skin tests with Dpt. In all the patients were performed following tests: BPT with histamine, serum specific IgE level against Dpt (sIgE Dpt), spontaneous basophil HR (spHR), anti-IgE depended basophil HR (aIgE HR), Dpt depended basophil HR (Dpt HR), sBPT with Dpt (sBPT Dpt). The positive results of sBPT Dpt were observed in 27 patients. Twenty six of them had the early¿ asthmatic response (EAR) at least, 19--dual asthmatic response (EAR and LAR) and isolated late asthmatic response (LAR) demonstrated only one patient. The correlation coefficient (r) between sIgE and Dpt HR was 0.4 p < 0.04, between sIgE and sBPT Dpt r = -0.4, p < 0.03, and between sBPT Dpt and Dpt HR r = -0.37, p < 0.05. The results showed a significant correlation between sIgE and Dpt HR, sIgE and sBPT Dpt, sBPT Dpt and Dpt HR and these tests appear to be of value in casual diagnosis of allergic bronchial asthma, but only sBPT makes possible to observe LAR.