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.

[Exacerbations in perimenstrual asthma. Clinical significance of peripheral blood eosinophilia and BMI]. / Zaostrzenia w astmie okolomiesiaczkowej. Znaczenie kliniczne eozynofilii w krwi obwodowej i BMI.

INTRODUCTION: Asthma is a heterogeneous disease characterized by lower airways' obstruction, caused by various factors. There are many asthma phenotypes. Lately, perimenstrual asthma (PMA) with a pattern of exacerbations before and during menstruation as well as obesity associated asthma have been a subject of particular scientific and clinical interest. MATERIAL AND METHODS: 30 women were qualified for this three-arm case-control study(women with a pattern of asthma exacerbations in the perimenstrual period, women with asthma but no perimenstrual exacerbations, healthy control group). All patients performed spirometry and assessed disease control using specific questionnaires. Peripheral blood counts with smear were also performed. RESULTS: PMA patients differ in a statistically significant way in respect of anthropometric measurements such as BMI: in PMA group 25.8±1.8; in non-PMA asthmatics 23.9 ±2.2; healthy control 23.1±1.5; p=0.018) and spirometry results (FEV1 [%]: 85.1 (36.3-113.0); in PMA asthmatics, 93.1 (81,6-109,7), in nonPMA group, p<0.05; 105.4 (108,3-119,0) in healthy control and Tiffeneau index [%]: 70.1 (41.2-98.1); in PMA vs 83.5 (59.6-94.4); in non-PMA asthmatics 93.1(81,8-97,5) in healthy control p<0.05; ). PMA asthmatics also complain of poorer disease control than non-PMA asthmatics. There were no differences in peripheral blood eosinophilia or CRP between studied groups, p>0.05). CONCLUSIONS: Asthma exacerbations are not associated with the effect of peripheral blood eosinophilia. Women with greater BMI are more predisposed to perimenstrual asthma.

Lung-heart clinical crosstalk in the course of COPD exacerbation.

INTRODUCTION: COPD exacerbation is a life-threatening condition with acute dyspnoea caused by respiratory or circulatory distress. The significance and co-presence of lung hyperinflation, bronchial obstruction, and changes in haemodynamics in the course of COPD exacerbation treatment have not been well described yet in course of a single study. Our aim was to evaluate the influence of COPD exacerbation treatment on bronchial obstruction, pulmonary hyperinflation, and possible changes of right and left ventricle haemodynamics in relation to the patient's clinical status. MATERIAL AND METHODS: A total of 40 patients (90% males), 67 ± 8 years old, with COPD were assessed pre- and post-exacerbation treatment by the following: respiratory function tests, transthoracic echocardiography, 6MWT, endothelin-1 (ET-1) and NT-proBNP serum concentrations, and MRC scale. RESULTS: A significant decrease in RV%TLC (%) and mean pulmonary artery pressure (PAPmean) [mm Hg] was observed: pre -RV%TLC: 64.3 ± 9.0; post-RV%TLC 60.6 ± 11.1; p = 0.03; pre-PAPmean: 41.2 ± 11.2; post-PAPmean: 39.1 ± 12.1; p = 0.029, coupled with a significant increase of FEV1 [L]-preFEV1: 1.0 ± 0.4, post-FEV1: 1.2 ± 0.5; p < 0.001. A trend for reduced right ventricle systolic pressure (RVSP) [mm Hg]: pre-treatment: 44.5 ± 12.9; post-treatment: 36.3 ± 14.3; p = 0.068 and ET-1 [fmol/ml]: pre-treatment: 1.7 ± 2.8; post-treatment: 1.3 ± 1.9; p = 0.076, but not for NT-proBNP was noticed. Improvement of both, 6MWT [m]: pre-treatment: 294 ± 132; post-treatment: 415 ± 102; p < 0.001 and MRC [pts.]: pre-treatment: 3.3 ± 0.8; post-treatment: 1.8 ± 0.9; p < 0.001, were noticed. 6MWT correlated with RV%TLC (p < 0.05; r = -0.46; r = -0.53; respectively) and FEV1 (p < 0.05; r = 0.55; r = 0.60, respectively) on admission as well as on discharge. There was no such correlation with RVSP or PAPmean. CONCLUSIONS: Pulmonary hyperinflation and bronchial obstruction may be reduced by effective COPD exacerbation treatment and are accompanied by clinical improvement. The mPAP reduction observed in the course of treatment was not correlated with the results of 6MWT and MRC score.

Perimenstrual asthma as a gynecological and pulmonological clinical problem.

Asthma is one of the most common chronic diseases of the respiratory system. It is estimated that up to 40% of asthmatic women of childbearing age may experience a cyclical exacerbation of asthmatic symptoms during the perimenstrual period, which is called perimenstrual asthma (PMA). The precise prevalence of this particular phenotype of asthma is difficult to determine due to a lack of explicit diagnostic criteria and appropriate epidemiological surveys. According to one of the best documented hypotheses regarding perimenstrual exacerbations of asthma, the impact of female steroid sex hormones on the function of the respiratory system and inflammations in the bronchi may play a central role in this phenomenon. Although the basic medical approach to PMA is similar to that used in other asthma phenotypes, unconventional methods of "experimental" treatment have also been tried. Unfortunately, current knowledge about the pathogenic mechanisms of this phenotype of asthma is incomplete and inconsistent, which justifies the need for further interdisciplinary studies with the participation of specialists in both gynecology and lung diseases. The knowledge thus acquired will help to individualize and focus future therapy on specific cellular and/or hormonal mechanisms to optimize asthma control in patients with PMA.

May smoking be considered as the most important factor that determines premature death after hospitalization due to COPD exacerbation? Preliminary data.

INTRODUCTION: COPD, cardiovascular diseases and cancer are smoking-related diseases that have been accepted as the leading causes of premature mortality worldwide. Nevertheless, smoking is still considered to be a risk rather than a prognostic factor for mortality. The aim of the study was to determine the most important factors in predicting the risk of premature death after effective hospital treatment of COPD exacerbation. MATERIAL AND METHODS: 34 consecutive patients hospitalized with COPD exacerbation were followed up and their post-hospitalization survival time was analyzed. Basic clinical data (BORG, MRC, BMI, pack-years and age) was collected. The following tests that were performed prior to discharge were assessed: 6MWT, spirometry, body plethysmography, diffusion capacity, transthoracic echocardiography (TEE) and whole night polysomnography. Routine laboratory and immunoenzymatic tests (hs-CRP, endothelin 1 (ET-1), NT-proBNP, IL-6, TNF-alfa) were analyzed. RESULTS: The average follow-up period was 15.1 ± 8.2 month. The mortality rate was 3/34 = 8.8%. Univariable analysis revealed significant differences that indicated a greater number of deaths at higher values of: pack-years (p = 0.02), BODE (p = 0.03), heart rate (HR) after 6MWT (p = 0.003), ET-1 (p = 0.04), but at lower values of TLCO/VA (p = 0.03) and 6MWT-distance (p = 0.006). Multivariable analysis revealed that only pack-years (p = 0.005) were predictive for mortality. CONCLUSIONS: Smoking history seems to have the strongest impact on short-term mortality after recovery from COPD exacerbation.

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.

Interleukin 17 and RANTES levels in induced sputum of patients with allergic rhinitis after a single nasal allergen challenge.

BACKGROUND: Interleukin 17 (IL-17) is produced by T(H)17 cells and was recently implicated in the development of the T(H)2 cell response. RANTES (regulated on activation of normal T cells expressed and secreted), among other chemokines, plays a crucial role in chemotaxis of eosinophils into airway mucosa. According to the "united airway" hypothesis, markers of inflammation in allergic diseases are elevated in the upper and lower airways. OBJECTIVE: To assess the impact of a single nasal allergen challenge on IL-17 and RANTES levels in induced sputum of patients with allergic rhinitis (AR). METHODS: Eighteen patients with a history of AR due to grass pollen confirmed by positive skin prick test results and 10 control subjects entered the study. Initially, all the patients underwent sputum induction. A single nasal placebo challenge was performed 24 hours later, with repeated sputum induction 24 hours after challenge. After 4 weeks of washout, these procedures were repeated with allergen challenge. Differential cell counts in sputum were determined, and concentrations of IL-17 and RANTES were measured by means of enzyme-linked immunosorbent assay. RESULTS: Levels of IL-17 and RANTES significantly increased in sputum of patients with AR after allergen (but not placebo) challenge (P = .03 and P = .007, respectively). Postallergen levels of both cytokines in sputum were positively correlated (r = 0.570, P = .02). Allergen challenge led to increased total inflammatory cell (P = .005) and eosinophil (P = .03) counts in induced sputum of patients with AR. CONCLUSIONS: Nasal allergen challenge induces the enhanced secretion of IL-17 and RANTES in the lower airways of nonasthmatic patients with AR.

[The comparison of reactions in skin prick test performed with the standardized lancet and the injection needle]. / Porównanie wyników punktowych testów skórnych wykonywanych za pomoca standaryzowanego lancetu oraz igly iniekcyjnej.

UNLABELLED: Achieving reproducible results with the skin prick test method depends on a certain amount of experience, the depth of skin penetration by the device which is used and reducing the number of false positive reactions caused by contamination of the device by allergen extract previously pricked. The aim of the study was to compare the results of SPT performed with "single puncture device" using lancet or injection needle with "multiple puncture device" using the same needle wiped in alcohol between pricks. MATERIAL AND METHODS: Twenty adult patients with seasonal allergic rhinitis with known sensitivity to grass pollen allergen and ten control subjects entered the study. SPT were applied to the volar surface of both forearms on two separate visits during which fixed sequence of pricking histamine, allergen and saline solutions (Allergopharma, Reinbeck, Germany) was maintained. On the first visit new device was used for each prick: injection needles on one forearm and lancets on the other. On a second visit (after a wash-out period of 4 weeks) injection needle changed between each prick on one forearm was compared with using the same needle wiped in alcohol between pricks on the other forearm. RESULTS: There was no statistical difference between the three tested methods for the size of wheel to histamine (p = 0.5), saline (p = 1) and allergen (p = 0.54) in group of SAR patients as well as for the size of wheel to histamine (p = 0.41) and saline (p = 1) in control subjects. Analysis of wheel diameters for histamine and allergen in group of SAR patients demonstrated comparable degrees of precision for all tested methods (CV%): there was no statistical difference between CV% achieved for the size of histamine (p = 0.73); as well as for allergen wheal (p = 0.32). CONCLUSIONS: The results of SPT achieved by using only one injection needle rinsed in alcohol for multiple pricks seem to have similar quality, being more economical than standard techniques in which puncture device is changed between each test.

Short-term CPAP treatment induces a mild increase in inflammatory cells in patients with sleep apnoea syndrome.

BACKGROUND: Nasal CPAP has been proven to be an efficient method of treating SAS patients without facial dysmorphism. However, it still remains a matter of debate why it is not universally well tolerated. The AIM OF THE STUDY was to evaluate the influence of initial CPAP treatment on nasal function in SAS patients. PATIENTS AND METHODS: Forty-two patients were consecutively included in a prospective clinical study and divided into the three following groups: 1) SAS subjects (26 patients qualifying for CPAP treatment), 2) First control group (C1) (9 patients with mild or moderate SAS, not willing to be treated with CPAP, AHI > 5 [n/h]), 3) Second control group (C2) (7 healthy subjects, AHI < or = 5). Nasal patency was measured by active anterior rhinomanometry (AAR) at recruitment and after a three-day CPAP treatment. After each AAR nasal lavage was obtained from both nostrils. Total inflammatory cell count (TCC) in each nasal lavage was then calculated in a Neubauer's chamber. RESULTS: Initial CPAP treatment caused a statistically significant rise of TCC in nasal lavage of SAS patients, when compared with initial values [n*10(5)/ml] (pre: 1.30, post: 1.92, p = 0.009). No significant differences (p > 0.05) were found both in initial TCC and nasal patency values among the three studied groups. CONCLUSIONS: SAS subjects present an unchanged nasal patency when compared to control subjects. Initial CPAP therapy might be responsible for evoking local nasal inflammation.

[The influence of sensitivity to fungal allergens on the development and course of allergic diseases of the respiratory tract]. / Wplyw wystepowania nadwrazliwosci na alergeny grzybów na rozwój i przebieg chorób alergicznych ukladu oddechowego.

Several epidemiological and diagnostic studies reported increasing prevalence of allergic reactivity to fungi assessed with the use of skin testing or IgE detection. The role of sensitization to fungi in relation to the prevalence and clinical importance in atopic patients remains largely unknown. Although an allergic reaction to fungal allergens is suggested as an important contributing factor in the development of respiratory symptoms, other mechanisms, such as increased exposure to fungal metabolites, mycotoxins and other compounds of immuno-suppressant or irritant properties, may also be important. Sensitivity to fungal allergens has been recognized as a risk factor for the development and persistence of asthma, asthma severity and potentially fatal asthma exacerbations, the increased number of episodes of respiratory arrest and admissions to intensive care unit. Thus far, the role of fungi as the dominant exogenous trigger of asthma has not been completely explored. Some authors suggest, that sensitization to fungal allergens is related with specific phenotype of severe asthma. It remains to be clarified, whether this association is caused by colonization of the airways with fungi or an extreme response to exogenous spores. This review critically discusses the present state of knowledge on the prevalence of IgE-mediated allergy to fungi, as well as the contribution of sensitization to fungi to the allergic manifestations, on the basis of the recent literature. We also try to assess the importance of these connections for the future treatment of allergic disorders of the respiratory tract.

[Functional links between the upper and lower airways in allergic diseases of the respiratory tract]. / Zaleznosci pomiedzy górnymi i dolnymi drogami oddechowymi w chorobach alergicznych ukladu oddechowego.

Traditionally, allergic rhinitis and bronchial asthma are described as distinct and separate entities. However, progress made in recent years has brought some great changes in the understanding of pathophysiology of allergic disorders. It has become clear that both of these disorders are characterised by similar triggers, inflammatory cells and mediators involved in their pathogenesis and treatment modalities. The link between these two airway disorders has led to the development of the so called "integrated airway hypothesis". According to this hypothesis allergic rhinitis and bronchial asthma are regarded as different facets of a generalised inflammatory process involving, although in a different degree, both the upper and lower airways. This review critically discusses the present state of knowledge on the links between the upper and lower airways in asthma and rhinitis on the basis of the recent literature and our own experience. We try to assess the importance of these links for the future diagnosis and treatment of allergic disorders of the respiratory tract.

[The role of interleukin 17A in inducing neutrophilic inflammation in the pulmonary tract]. / Rola interleukiny 17A w rozwoju zapalenia neutrofilowego w ukladzie oddechowym.

UNLABELLED: Interleukine 17A is a proinflammatory cytokine produced by activated memory T-cells, which indirectly connects these cells with the enhanced accumulation of the polymorphonuclear cells in the site of inflammation. AIM OF THE STUDY: The aim of this paper is to present the current knowledge on the role of interleukin 17A in the pathogenesis of inflammatory diseases of the pulmonary tract. IL-17A-induced accumulation of neutrophils in pulmonary tissues proceeds mainly through its influence on stomal cells which produce larger amounts of neutrophilic chemotactic factors (CXC chemokines) as well as granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF, GM-CSF), leading to the enhanced maturing of CD34+ progenitor cells and their further differentiation into neutrophils in bone marrow. CONCLUSIONS: Although neutrophilic inflammation, which is a consequence of IL-17A activity, is an important element of pulmonary host defence, the prolonged action of this cytokine directed on the proliferation, maturing and chemotaxis of neutrophils to the pulmonary tract may contribute to chronic tissue destruction. Scientific research supplies proves, that this cytokine is co-responsible for the development of many functional abnormalities (e.g. bronchial hyperresponsiveness, enhanced mucus secretion, airway remodeling) in course of diseases such as: chronic bronchitis, chronic obstructive pulmonary disease and bronchial asthma.

[Nasal provocation tests in the diagnosis of allergic rhinitis]. / Próby prowokacyjne donosowe w diagnostyce alergicznego niezytu nosa.

Allergic rhinitis is a frequent immunological disease affecting about 10-25% of the total population. The pathogenesis of allergic rhinitis is presumed to involve an IgE-mediated mechanism. Careful patient history, together with the skin prick test or RAST, usually allows an easy diagnosis of allergic rhinitis. In other cases it may be necessary to confirm diagnosis by the nasal provocation test. Different methods of provocation and measurement of nasal responses have been used in recent years. Scoring of the severity of clinical symptoms is too subjective to be clinically useful and should therefore be supplemented by one of the objective measurement techniques, such as anterior rhinomanometry. Additional analysis of nasal cytologic findings and determination of biomarkers in nasal secretions can be a critical tool in the evaluation of pathophisiology of allergic rhinitis. We critically discuss indications and contraindications for nasal challenges and review current techniques of provocation. We also provide various methods of assessment of nasal responses. The included examples of nasal provocation tests protocols may be helpful in introducing nasal provocation tests into everyday clinical practice.

[The role of interleukin 17 cytokine family in inducing allergic inflammation in the pulmonary tract]. / Rola cytokin z rodziny interleukiny 17 w rozwoju alergiczxnej reakcji zapalnej w ukladzie oddechowym.

IL-17 family is a group of proinflammatory cytokines produced by activated memory T-cells. These cytokines play an important role in the development of cellular and humoral mechanisms of immunological responses lying at the basis of allergic disorders. The aim of this paper is to present the current knowledge on the role of interleukin 17 cytokine family in the pathogenesis of allergic disorders of the respiratory tract. IL-17A (as well as IL-17F) plays role in the development of airway hyperresponsiveness through activation of allergen-specific T-cells. Levels of IL-17A are elevated in sputum of asthmatic patients and correlate with airway hyperresponsiveness to methacholine. However, it remains fact, that the main effect of IL-17A in the pulmonary tract is recrutation of polymorphonuclear leukocytes, depending on CXC chemokine release from stromal cells. IL-17E evokes different immunological responses. This cytokine participates in the development of Th2-cell-dependent immunological response and the coexisting pathological tissue changes. These actions take place mainly through the induction of synthesis of the Th2 cell-derived cytokines (IL-4, IL-5, IL-13) and the development of eosinophilic inflammation. It is thought, that the character of the immunological response evoked by different cytokines of IL-17 family depends on the differences between the spatial structure of their fragments including disulfide bridges and that these differences determine their receptor interactions and biological functions.