ERS/ESTS statement on the management of pleural infection in adults.

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice.

Oral immunotherapy in children with a food allergy-Where do we stand? - Review.

The number of hospitalisations due to an anaphylactic reaction to food is continuously increasing. Therefore, there is an urgent need to seek effective therapy. Currently, the only way to treat food allergies is to avoid allergens and to administer intramuscular adrenaline if an accidental allergen intake occurs. The only causal therapeutic strategy is specific oral immunotherapy. An increasing amount of data confirms this therapy's effectiveness and safety, but the results remain inconclusive due to the lack of long-term follow-up. In this state-of-the-art review, we briefly summarise the latest placebo-controlled randomised controlled trials on oral immunotherapy (OIT) to treat food allergy. During the paper's review, we asked the following questions: does the therapy permanently increase the amount of allergen consumed without symptoms? Does it significantly increase or decrease the occurrence of severe systemic reactions - requiring the administration of adrenaline or hospitalisation? Many authors describe outcomes such as an increase in the amount of allergen that can be safely ingested; however, significant clinical benefits such as decreased hospitalisations or anaphylaxis incidence are rarely included in the results. To date, there is no unified protocol of therapy, which makes comparisons between studies difficult because of significant differences in types, doses, and routes of administration of the allergen, timeline for up-dosing and maintenance, duration of the therapy, and primary outcomes of OIT.

Impact of Factors Secreted by Tumor Cells on Response of Pleural Mesothelial Cells to Different Sclerosing Agents in an In Vitro Model.

BACKGROUND Chemical pleurodesis is one of the major therapeutic options for patients with recurrent malignant pleural effusion. Mesothelial cells are considered to play a pivotal role in the response to different chemical compounds (sclerosants) used for pleurodesis. Malignant cells might have an impact on the mesothelial response to applied sclerosing agents and, in consequence, on the efficacy of pleurodesis. We aimed to evaluate the impact of cancer cell paracrine on mesothelial cell response to different sclerosing agents. MATERIAL AND METHODS The study used mesothelial cell (MeT-5A) cultures stimulated with sclerosing agents (talc, doxycycline, iodopovidone, and TGF-ß for 24 h) in the presence or absence of supernatants from adenocarcinoma cultures (HCC827). The mesothelial mRNA expression and protein levels of IL-6, IL-8, and TGF-ß was assessed. Further, lung fibroblasts were cultured with and without cell supernatants from previously established cell cultures for 24 h. Then, concentration of soluble collagen was evaluated in culture supernatants. RESULTS The exposure of mesothelial cells to sclerosants decreased the concentration of IL-6 and IL-8 protein. The addition of mediators secreted by adenocarcinoma altered the inflammatory response of the mesothelial cells to sclerosing agents. IL-8 concentration in cultures stimulated with talc and adenocarcinoma supernatant was higher compared to cultures stimulated with talc only. The exposure of lung fibroblasts to supernatant from mesothelial cell (with or without adenocarcinoma) did not affect collagen secretion. CONCLUSIONS An addition of soluble factors produced by adenocarcinoma altered the inflammatory response of the pleural mesothelial cells after stimulation with sclerosing agents. Our observations suggest that the tumor paracrine effect affects biological pathways of pleurodesis.

RNA-Seq Analysis of UPM-Exposed Epithelium Co-Cultivated with Macrophages and Dendritic Cells in Obstructive Lung Diseases.

BACKGROUND: Elevated concentrations of airborne pollutants are correlated with an enlarged rate of obstructive lung disease morbidity as well as acute disease exacerbations. This study aimed to analyze the epithelium mRNA profile in response to airborne particulate matter in the control, asthma, and COPD groups. RESULTS: A triple co-culture of nasal epithelium, monocyte-derived macrophages, and monocyte-derived dendritic cells obtained from the controls, asthma, and COPD were exposed to urban particulate matter (UPM) for 24 h. RNA-Seq analysis found differences in seven (CYP1B1, CYP1B1-AS1, NCF1, ME1, LINC02029, BPIFA2, EEF1A2), five (CYP1B1, ARC, ENPEP, RASD1, CYP1B1-AS1), and six (CYP1B1, CYP1B1-AS1, IRF4, ATP1B2, TIPARP, CCL22) differentially expressed genes between UPM exposed and unexposed triple co-cultured epithelium in the control, asthma, and COPD groups, respectively. PCR analysis showed that mRNA expression of BPIFA2 and ENPEP was upregulated in both asthma and COPD, while the expression of CYP1B1-AS1 and TIPARP was increased in the epithelium from COPD patients only. Biological processes changed in UPM exposed triple co-cultured epithelium were associated with epidermis development and epidermal cell differentiation in asthma and with response to toxic substances in COPD. CONCLUSIONS: The biochemical processes associated with pathophysiology of asthma and COPD impairs the airway epithelial response to UPM.

The expression of IL17RA on sputum macrophages in asthma patients.

IL-17A and IL-25 (IL-17 cytokines family) play an important role in the development of asthma, and allergy. Both cytokines act by binding to heterodimeric receptors with IL17RA as a common subunit. This receptor is found on macrophages, and some other cell types. The aim of the study was to determine the expression of IL17RA on asthmatic and control macrophages from induced sputum (IS) with the regard to IL-17/IL-25 background and relation to clinical features of the disease. We found an elevated expression of IL17RA on sputum macrophages in asthma patients vs controls. A characteristic sputum profile of atopic asthmatic was as follows: high CD206 + IL17RA + macrophage percentage, elevated IL-25 level and low CD206 + IL17RA- macrophage percentage. Based on the above results, it seems that CD206 + sputum macrophages are the effector cells that express common subunit of the receptor for IL-17A and IL-25 in asthma. This may be related to the Th2-dependent environment in asthma and increased concentrations of IL-25 and IL-13 as well as eosinophils in the airways. To our knowledge, our study provides the first data on a possible link between immunological reaction orchestrating CD206 + expressing sputum macrophages and IL-25 via IL17RA pathway in the asthmatic airways.

Does bronchial hyperresponsiveness predict a diagnosis of cough variant asthma in adults with chronic cough: a cohort study.

Bronchial hyperresponsiveness is a typical, but non-specific feature of cough variant asthma (CVA). This study aimed to determine whether bronchial hyperresponsiveness may be considered as a predictor of CVA in non-smoking adults with chronic cough (CC). The study included 55 patients with CC and bronchial hyperresponsiveness confirmed in the methacholine provocation test, in whom an anti-asthmatic, gradually intensified treatment was introduced. The diagnosis of CVA was established if the improvement in cough severity and cough-related quality of life in LCQ were noted.The study showed a high positive predictive value of bronchial hyperresponsiveness in this population. Cough severity and cough related quality of life were not related to the severity of bronchial hyperresponsiveness in CVA patients. A poor treatment outcome was related to a low baseline capsaicin threshold and the occurrence of gastroesophageal reflux-related symptoms. In conclusion, bronchial hyperresponsiveness could be considered as a predictor of cough variant asthma in non-smoking adults with CC.

Periostin concentration in exhaled breath condensate in children with mild asthma.

OBJECTIVE: Periostin is considered to be a marker of eosinophilic inflammation in patients with asthma. However, there are no literature data on exhaled breath condensate (EBC) periostin level in pediatric patients with asthma. The aim of this study was to analyze EBC periostin concentration in children with mild asthma and to evaluate the potential usefulness of EBC periostin level as a biomarker for the disease. METHODS: EBC and serum periostin concentrations were measured by enzyme-linked immunosorbent assay in 23 children with asthma and 23 healthy controls. RESULTS: EBC periostin concentration was 250- to 780-fold lower than that found in serum. No significant differences between serum nor EBC periostin concentration in asthmatics and the control group were showed. The comparison between children with Th2 and non-Th2 type of asthma did not show significant differences in periostin concentration, both in serum and EBC. Serum periostin concentration inversely correlated with BMI and age not only in asthma patients but also in controls. CONCLUSIONS: In children with mild asthma, periostin may be measured not only in serum but also in EBC. The low periostin level in patients with mild asthma and lack of difference between asthmatic subjects and controls indicate that EBC periostin may not be useful as an asthma biomarker in this group.

Is the composition of exhaled breath condensate a key to explain the course of COVID-19 in children?

INTRODUCTION: The relative resistance of children to severe course of the novel coronavirus infection remains unclear. We hypothesized that there might be a link between this phenomenon and observation from our previous studies concerning an inhibitory or cytotoxic effect of exhaled breath condensate (EBC) on endothelial cell cultures in children. AIM: Since we could not find any data on the similar effect caused by EBC in adults, the aim of our study was to evaluate and compare the biological activity of EBC in adults and children in an experimental in vitro model. Furthermore, in order to identify a putative agent responsible for these properties of EBC in children, we attempted to analyse the composition of selected EBC samples. MATERIAL AND METHODS: The influence of EBC samples on metabolic activity of endothelial cell line C-166 was assessed using colorimetric tetrazolium salt reduction assay (MTT assay). Selected EBC samples were fractionated using size exclusion chromatography and subjected to mass spectrometry analysis. RESULTS: Exhaled breath condensates in healthy children, but not in adults, revealed a cytotoxic effect on in vitro cell cultures. This effect was most significant in condensate fraction, which contained a prominent 4.8 kDa peak in the mass spectra. CONCLUSIONS: Breath condensates of healthy children contain the factor which reveals the inhibitory/cytotoxic effect on endothelial cell cultures. Although the physiological role of this agent remains unclear, its identification may potentially be useful in ongoing research on SARS-CoV-2/COVID-19.

Epithelial-macrophage-dendritic cell interactions impact alarmins expression in asthma and COPD.

In the respiratory system macrophages and dendritic cells collaborate as sentinels against foreign particulate antigens. The study used a triple-cell co-culture model, utilizing nasal epithelial cells, along with: monocyte derived macrophages (moMφs), and monocyte derived DCs (moDCs). Cell cultures from 15 controls, 14 asthma and 11 COPD patients were stimulated with IL-13 and poly I:C for 24 h. Co-cultivation of epithelial cells with moMφs and moDCs increased TSLP level only in asthma and the effect of IL-13 and poly I:C stimulation differed in all groups. Asthma epithelial cells expressed higher level of receptors TSLPR, ST2 and IL-17RA than controls and increased number of ST2 + ciliated and IL17RA + secretory cells. Cytokine expression in respiratory epithelium may be influenced by structural and immunological cell interaction. TSLP pathway may be associated with secretory, while IL-33 with ciliated cells. The impaired function of respiratory epithelium may impact cell-to-cell interactions in asthma.

Expression of TSLP and IL-33 receptors on sputum macrophages of asthma patients and healthy subjects.

Objective: Local cytokine milieu (especially Th2 inflammatory type) secreted into the asthmatic airways affect the alternative activated macrophages polarization (M2). TSLP and IL-33 are important alarmins of allergic response associated with Th2 inflammation. The aim of the study was to investigate the expression of the receptors for epithelial derived cytokines: TSLP (TSLPR) and IL-33 (ST2) on induced sputum CD206 positive macrophages from asthma and healthy subjects and analyze the relationships between these receptors and clinical features of the disease. Methods: Immunofluorescence staining for CD206 and TSLPR or ST2 on sputum macrophages was performed in 20 adult patients with stable asthma - 75% with atopy (3 intermittent, 12 mild-to-moderate, 5 severe, of which 11 were on biological anty-IgE treatment) and 23 healthy adult controls - 48% with atopy. Results: Our study demonstrated an increased expression of TSLP and IL-33 receptors on bronchial CD206 positive macrophages in asthma group. TSLPR but not ST2 had also greater expression on CD206 negative macrophages in asthma patients. Increased expression of both investigated receptors was related to longer disease duration and impaired lung function. We observed increased count of CD206lowTSLPhigh macrophages as well as positive correlation of these cells with total serum IgE in patients with atopy. Conclusions: The macrophage response during allergic reaction is likely to be connected with TSLP but rather not with IL-33 action. Our study indicates an important role of crosstalk between macrophages, TSLP and IL-33 in asthma pathophysiology.

A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study.

BACKGROUND: Pirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles. METHODS: This was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion. RESULTS: A total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75-30) months and from diagnosis to start of pirfenidone treatment was 6 (2-23) months. Patients were followed on treatment for a median of 17 (12-22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient's own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was -20 ml (-200-100) and during the second year was -120 ml (-340-30). Over a study period, 33 patients (10.75%) died. CONCLUSIONS: The PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.

Chronic cough related to the upper airway cough syndrome: one entity but not always the same.

PURPOSE: Upper airway cough syndrome (UACS), described as chronic cough (CC) associated with allergic (AR), non-allergic rhinitis (NAR) or chronic rhinosinusitis (CRS), is one of the major causes of CC. We aimed to characterize a cohort of UACS patients with special attention to differences between patients with AR and NAR. METHODS: A prospective analysis of clinical data of patients, diagnosed with UACS between 2015 and 2018. RESULTS: There were 143 patients diagnosed with UACS, median age 52 years, women predominance (68.5%), The group comprised of 59 (41%) AR and 84 (59%) NAR subjects, CRS diagnosed in 17 (12%). Median cough duration: 48 months (IQR 24-120), median cough severity (VAS)-60 mm (IQR 42-78), median Leicester Cough Questionnaire (LCQ) score-11.3 (IQR 8.7-13.7), never-smokers: 70%. The most common symptoms: PND (62%), rhinorrhea (59%), nasal congestion (54%), abnormalities of sinus CT: septum deviation (62%), turbinates hypertrophy (53%), mucosal thickening (53%). UACS as the only cause of CC, was presented in 20 patients (14%). We found no differences between patients with AR and NAR in terms of age, gender, duration and severity of cough, BMI, blood eosinophil count, total IgE and FeNO. AR was associated with higher comorbidity of asthma than NAR (54% vs 35%, p = 0.019). Abnormalities in sinus CT scan were more frequently found in patients with NAR than AR (p = 0.018). CONCLUSION: NAR is the most common upper airway disease associated with UACS. Clinical characteristics of UACS patients with AR and NAR are similar with only minor differences between these groups. It seems reasonable to plan further studies concerning relationship of NAR and cough sensitivity, also in terms of potential similar neurogenic mechanism.

mRNA expression profile of bronchoalveolar lavage fluid cells from patients with idiopathic pulmonary fibrosis and sarcoidosis.

BACKGROUND: Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two most frequent forms of interstitial lung diseases (ILDs). Cellular and biochemical composition of bronchoalveolar lavage fluid (BALf) was shown to reflect the fibrotic changes in the lung. However, the usefulness of BALf cellular profile evaluation in the diagnosis of ILDs is limited. The aim of the study was a multivariate, molecular analysis of BALf cells from IPF and sarcoidosis patients. METHODS: Transcriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 21 samples: 9 IPF and 12 sarcoidosis. The mRNA expression for the most significantly differentiating genes was evaluated by real-time PCR in 32 samples (11 IPF and 21 sarcoidosis). RESULTS: The number of genes differentially expressed between IPF and sarcoidosis groups was 4832 (13359 probesets). Cluster analysis indicated that sarcoidosis BALf cells are characterized by increased mRNA expression of genes associated with ribosome biogenesis. Clusters formed by genes with changed mRNA expression in IPF samples were implicated in the processes of cell adhesion and migration, metalloproteinase expression and negative regulation of cell proliferation. The GO analysis indicated that predominant biological processes associated with the differential mRNA gene expression of BALf cells were upregulation of neutrophils in IPF and lymphocytes in sarcoidosis. CONCLUSIONS: Analysis of BALf from sarcoidosis and IPF showed highly different mRNA profile of cells. The most important biological processes observed at the molecular level in BALf cells were associated with ribosome biogenesis and proteasome apparatus in sarcoidosis and neutrophilic dysfunction in IPF.

Chemical pleurodesis - a review of mechanisms involved in pleural space obliteration.

Chemical pleurodesis is a therapeutic procedure applied to create the symphysis between the parietal and visceral pleura by intrapleural administration of various chemical agents (e.g. talk, tetracycline, iodopovidone, etc.). The two major clinical conditions treated with chemical pleurodesis are recurrent pleural effusion (PE) and recurrent spontaneous pneumothorax. Although the history of chemical pleurodesis began over a century ago, detailed data on the mechanisms of action of sclerosing agents are highly incomplete. The following article aims to present the state of knowledge on this subject.It is believed that mesothelial cells are the main structural axis of pleurodesis. In response to sclerosing agents they secrete a variety of mediators including chemokines such as interleukin 8 (IL-8) and monocyte chemoattractant protein (MCP-1), as well as growth factors - vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and transforming growth factor- ß (TGF-ß). Numerous data suggest that intact mesothelial cells and the above cytokines play a crucial role in the initiation and maintenance of different pathways of pleural inflammation and pleural space obliteration.It seems that the process of pleurodesis is largely nonspecific to the sclerosant and involves the same ultimate pathways including activation of pleural cells, coagulation cascade, fibrin chain formation, fibroblast proliferation and production of collagen and extracellular matrix components. Of these processes, the coagulation cascade with decreased fibrinolytic activity and increased fibrinogenesis probably plays a pivotal role, at least during the early response to sclerosant administration.A better understanding of various pathways involved in pleurodesis may be a prerequisite for more effective and safe use of various sclerosants and for the development of new, perhaps more personalized therapeutic approaches.

Relationship between Blood and Induced Sputum Eosinophils, Bronchial Hyperresponsiveness and Reversibility of Airway Obstruction in Mild-to-Moderate Chronic Obstructive Pulmonary Disease.

Blood eosinophilia has been proposed as a surrogate marker for airway eosinophilia and as a predictor of treatment response in chronic obstructive pulmonary disease (COPD). The aim of the study was to assess the relationship between blood and sputum eosinophils and to investigate the association between blood and sputum eosinophil count and clinical features of mild-to-moderate COPD. We performed a retrospective analysis of blood and sputum eosinophil count, as well as demographic and lung function data in a cohort of 90 stable, steroid-naive (Global Initiative for Chronic Obstructive Lung Disease 1 or 2) COPD patients and 20 control subjects. Blood and sputum eosinophil count did not correlate both in patients with COPD (r = -0.04 p = 0.705) and in controls (r = 0.05, p = 0.838). Sputum eosinophilia (≥3%) was present in 40% of COPD patients. The median blood eosinophil count in patients with COPD was 180 (interquartile range 90-270)/µL; patients with low blood eosinophils (<180/µL) did not differ from those with high blood eosinophils (≥180/µL) in terms of forced expiratory volume in 1 second, bronchial reversibility or hyperresponsiveness. This was also the case when COPD patients with and without sputum eosinophilia were compared. At the same time, positive bronchial reversibility and positive bronchial hyperresponsiveness were observed in 2 (11%) COPD patients with high blood eosinophils and in 1 (5%) patient with sputum eosinophilia. There was a weak, albeit significant correlation (r = 0.22 p = 0.041) between blood eosinophil count and age in patients with COPD. Peripheral eosinophil count poorly reflects sputum eosinophils and lung function in stable steroid-naive mild-to-moderate COPD patients.

Mishandling of pMDI and DPI inhalers in asthma and COPD - Repetitive and non-repetitive errors.

BACKGROUND: Pharmacological treatment of asthma and chronic obstructive pulmonary disease (COPD) is based mainly on inhaled medications. There is a continuous need to examine and train patients in their inhalation technique. The objective of the presented study is to determine whether the errors which patients made during inhalations are repetitive, and therefore easier to eradicate, or rather accidental, hence require more attention and effort from the health care professionals. METHODS: It was a prospective, cohort study which included adults with asthma or COPD, who have used at least one inhaler daily on a regular basis. Inhalation technique was evaluated twice in a six months interval basing on a list of the most common errors in the inhalation technique. There was no training of inhalation skills between visits. RESULTS: There were 92 patients (46 asthmatics, 46 with COPD; median age 66 years, median duration of the disease 10 years) included into the analysis. 92% of patients made at least one error during their inhalation. Among pMDI users the most common device mishandlings were: no or too short breath-holding after inhalation (60% of the patients during the first visit; 50% during the 2nd), too rapid and too forceful inhalation (52%; 61%) and lack of exhalation before the use of the medicine (48%; 43%). Among the DPI users, the most numerous errors were: no or too short (less than 3 s) breath-holding after inhalation (62%; 55%) and slow and not forceful enough inhalation (38%; 36%). When comparing the mishandlings in the inhalation technique conducted during the first and second visit the majority of the errors conducted by the patients were repetitive. However, some errors such as too early termination of inhalation (p = 0.016), inhalation through the nose during actuation (p = 0.002) among pMDI users and lack of expiration before inhalation (p = 0.027) among DPI users, were non-permanent. CONCLUSIONS: Improper inhalation technique is very common and the majority of errors made in inhalation technique are repetitive. This emphasizes the role of an ongoing verification and training of a proper inhalation technique in all patients that are regularly treated with inhalers.

Menopausal asthma-much ado about nothing? An observational study.

OBJECTIVE: Menopausal asthma is considered a distinct asthma phenotype. Our aim was to identify potential specific features of asthma in postmenopausal women in a cohort of Polish females. METHODS: Asthma severity and control, pulmonary function, exhaled nitric oxide (FENO), peripheral blood and induced sputum (IS) differential cell count were compared in three groups: women with premenopausal asthma (group 1), menopausal women with pre-existing asthma (group 2A) and menopausal women with asthma onset in the perimenopausal or menopausal period (group 2B). RESULTS: We enrolled 27 women to group 1, 13 to group 2A and 16 to group 2B. Asthma severity and control, blood eosinophil count and FENO did not differ among the groups. Menopausal women had a higher incidence of irreversible airway obstruction (84.6% in group 2A and 56.2% in group 2B vs. 22.2% in group 1, p < 0.001 and p = 0.03, respectively). The proportion of patients with sputum eosinophilia was highest in menopausal women with pre-existing asthma, although the difference did not reach statistical significance (88.9% in group 2A vs. 66.7% in group 2B and 65.0% in group 1, respectively, p = 0.86). CONCLUSIONS: Menopausal women with asthma are characterized by an increased incidence of irreversible airway obstruction regardless of disease duration. This may indicate that age may contribute to pulmonary function impairment in asthmatic women independently of their hormonal status at the time of asthma diagnosis. Our results failed to confirm the presence of specific asthma features which would allow to distinguish the phenotype of menopausal asthma.

Patterns of pleural pressure amplitude and respiratory rate changes during therapeutic thoracentesis.

BACKGROUND: Although the impact of therapeutic thoracentesis on lung function and blood gases has been evaluated in several studies, some physiological aspects of pleural fluid withdrawal remain unknown. The aim of the study was to assess the changes in pleural pressure amplitude (Pplampl) during the respiratory cycle and respiratory rate (RR) in patients undergoing pleural fluid withdrawal. METHODS: The study included 23 patients with symptomatic pleural effusion. Baseline pleural pressure curves were registered with a digital electronic manometer. Then, the registrations were repeated after the withdrawal of consecutive portions of pleural fluid (200 ml up to 1000 ml and 100 ml above 1000 ml). In all patients the pleural pressure curves were analyzed in five points, at 0, 25%, 50%, 75% and 100% of the relative volume of pleural effusion withdrawn in particular patients. RESULTS: There were 11 and 12 patients with right sided and left sided pleural effusion, respectively (14 M, 9F, median age 68, range 46-85 years). The most common cause of pleural effusion were malignancies (20 pts., 87%). The median total volume of withdrawn pleural fluid was 1800 (IQR 1500-2400) ml. After termination of pleural fluid withdrawal Pplampl increased in 22/23 patients compared to baseline. The median Pplampl increased from 3.4 (2.4-5.9) cmH2O to 10.7 (8.1-15.6) cmH2O (p < 0.0001). Three patterns of Pplampl changes were identified. Although the patterns of RR changes were more diversified, a significant increase between RR at baseline and the last measurement point was found (p = 0.0097). CONCLUSIONS: In conclusion, therapeutic thoracentesis is associated with significant changes in Pplampl during the respiratory cycle. In the vast majority of patients Pplampl increased steadily during pleural fluid withdrawal. There was also an increase in RR. The significance of these changes should be elucidated in further studies. TRIAL REGISTRATION: ClinicalTrial.gov, registration number: NCT02192138 , registration date: July 1st, 2014.

Severe mitral stenosis secondary to eosinophilic granulomatosis resolving after pharmacological treatment.

We present a case of 44-year-old woman who underwent effective pharmacological treatment of severe mitral stenosis. The patient was hospitalized due to rapidly progressive dyspnea. Her medical history included asthma, perennial rhinitis, and nasal polyps. Echocardiography showed a mass of the left ventricle involving the mitral valve; cardiac MRI suggested acute endocarditis. Severe peripheral blood eosinophilia was found. Eosinophilic granulomatosis with polyangiitis was diagnosed; treatment with prednisone and cyclophosphamide was started. Despite the clinical improvement, severe mitral stenosis persisted, surgical treatment was planned. However, evaluation after 6 cycles of cyclophosphamide pulse therapy revealed a significant regression of the valvular disease.

Expression of Inflammatory Mediators in Induced Sputum: Comparative Study in Asthma and COPD.

Asthma and COPD are the most common obstructive lung diseases characterized by inflammation in the lower airways which contribute to airflow limitation. Different inflammatory mediators are thought to play a key role in these diseases. This study was conducted in 13 patients with asthma, 12 patients with COPD, and 13 control subjects. The expression of mRNA of IL-6, IL-13, CXCL8, TSLP, IL-33, IL-25, IL-17, ECP, mast cell tryptase, CCL24, and CCL26 was assessed in induced sputum cells by real time PCR. We found that CXCL8 was strongly related to the neutrophil percentage but differed significantly in COPD and asthma patients. The expression of IL-17 was lower in patients with atopic asthma compared to non-atopic asthma. The percentage of macrophages correlated negatively with the expression of mast cell tryptase and ECP in COPD, and with CXCL8 in asthma. The expression of ECP correlated negatively with the severity of COPD symptoms measured by CAT. We conclude that asthma and COPD demonstrate a significant overlap in the airway cytokine profile. Thus, differentiation between the two diseases is difficult as based on a single cytokine, which suggests the coexistence of phenotypes sharing a common cytokine network in these obstructive lung diseases.