Macrolide antibiotics are known to exert anti-inflammatory actions
in vivo, including certain effects in COPD patients. In order to investigate the immunomodulatory profile of activity of macrolide ...antibiotics, we have studied the effects of azithromycin, clarithromycin, erythromycin and roxithromycin on the
in vitro production of a panel of inflammatory mediators from cells isolated from human, steroid-naïve, COPD sputum samples. Macrolide effects were compared to three other commonly used anti-inflammatory compounds, the corticosteroid dexamethasone, the PDE4 inhibitor, roflumilast and the p38 kinase inhibitor, SB203580. Three of the four tested macrolides, azithromycin, clarithromycin and roxithromycin, exhibited pronounced, concentration-related reduction of IL-1β, IL-6, IL-10, TNF-α, CCL3, CCL5, CCL20, CCL22, CXCL1, CXCL5, and G-CSF release. Further slight inhibitory effects on IL-1α, CXCL8, GM-CSF, and PAI-1 production were also observed. Erythromycin was very weakly active. Qualitatively and quantitatively, macrolides exerted distinctive and, compared to other tested classes of compounds, more pronounced immunomodulatory effects, particularly in terms of chemokine (CCL3, CCL5, CCL20, CCL22, and CXCL5), IL-1β, G-CSF and PAI-1 release. The described modulation of inflammatory mediators could potentially contribute to further definition of biomarkers of macrolide anti-inflammatory activity in COPD.
Tobacco consumption is one of the most common preventable cause of premature deaths worldwide. Persisting effects of exposure to tobacco smoke on children and adolescents are apparent during ...pregnancy and in early infancy, passive exposure to environmental tobacco smoke in home and elsewhere, and active smoking during adolescence. While, lung development in these stages of growth is not complete, tobacco smoke puts children and adolescents in danger of severe respiratory diseases and may interfere with the growth of their lungs. Active tobacco consumption by adolescents may have immediate adverse health outcomes such as addiction, impaired lung growth or reduced lung function. Much of the current evidence comes from longitudinal and cross-sectional longitudinal observational studies and propose that the strongest associations with smoke exposure are in the pregnancy and early childhood. The association of nicotine with respiratory system among children and adolescents is less clearly understood and the evidence primarily comes from in vitro and animal studies.
Recently, the Respiratory Effectiveness Group highlighted the role of real-world evidence (RWE) in (i) filling knowledge gaps, (ii) extending the implementation of findings from Randomized controlled ...trials in heterogeneous populations or healthcare systems, and (iii) providing evidence to generate clinical practice guidelines. 3 Prospective, systematic RWE from registries are considered to provide a broadly applicable source of knowledge compared with retrospective approaches. 6 However, there is still a lack of such registries in the allergy field. 7 In this context, a new hierarchy of AIT RWE that ranks pragmatic trials and registry data at the highest level of evidence was proposed in a recent European Academy of Allergy and Clinical Immunology (EAACI) position paper. 6 Considering these factors, a Task Force (TF) was created under the academic support of EAACI to develop an AIT Adverse Events Registry (ADER). The main objectives of the registry are (I) to assess systemic and local AEs occurring during regular clinical practice in real-life settings, (II) to collect data and evaluate patient characteristics and AIT practice among countries (expected to differ substantially), (III) to identify independent factors associated with AE, and (IV) to use ADER as a model for AIT pharmacovigilance that could be subsequently expanded to other European countries. Could not be well circumscribed & not itchy) Asthma Blood pressure decreased (suspicion of hypotension, but blood pressure not measured) Bronchospasm Chest discomfort Chest tightness Conjunctivitis allergic (eye swelling, pruritus, hyperaemia) Cough Diarrhoea Dysphagia (swallowing difficulty/disorder) Dysphonia (voice alteration) Dyspnoea Dizziness Erythema (not at injection/application site but localized abnormal redness of the skin without any raised lesions) Fatigue Flushing (generalised flushing) Generalised erythema Headache Hypotension (blood pressure measured systolic <90mmHg or >30% below baseline value) Laryngeal oedema (objective glottic or vocal cord oedema) Loss of consciousness Nausea Pruritus generalized Rhinitis allergic (rhinorrhoea, sneezing, nasal congestion/itching) Sensation of foreign body Syncope (vasovagal, fainting) Tachycardia (significant increase of the cardiac rhythm) Urticaria (generalized) Vomiting Wheezing Local reactions Subcutaneous and Venom Immunotherapy Local twinkling, itching, redness of the skin Large local reaction of the skin Sublingual Immunotherapy Twinkling, itching, redness in oral cavity Oedema in oral cavity In conclusion, we consider ADER as a first effort to create a multinational network of centres practicing AIT and exchanging best practice parameters.
Chronic obstructive pulmonary disease (COPD), an increasing global health problem, may be complicated by acute atherothrombotic events. Although systemic inflammation plays the leading role in ...atherothrombotic processes, platelet activation and increased coagulation together with oxidative stress can significantly exacerbate atherosclerosis in COPD patients. In this study we determined platelet count, mean platelet volume (MPV) and classical markers of systemic inflammation - serum C-reactive protein (CRP), white blood cell (WBC) count and the relative proportion of segmented neutrophils in COPD patients, and compared them to those from the healthy controls. The most important and novel finding of this study was that patients with COPD had a significantly increased platelet count, along with a reduced MPV when compared to healthy controls (286 vs. 260 × 109/l; 9.6 vs. 8.7 fL, respectively). Cigarette smoking had no influence on these results. The presence of systemic inflammation was clearly proved by the increase in classical inflammatory markers (CRP, WBC and segmented neutrophil count).
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to test the hypothesis that glutathione- S-transferase (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were determined by DNA methods and GST ...activity spectrophotometrically in older male Caucasian Croats (non- -smokers, ex-smokers, and smokers) with stable COPD (n = 30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1 null genotypes were not disease associated. Serum GST was not associated with GST genotypes and COPD or smoking history in our study subjects. Conclusions drawn from the study should be further supported and clarified by studies with larger sample sizes.
Summary
Background
No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory ...hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients.
Methods
A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium). Short-term treatment ineffectiveness was assessed as a composite measure comprising COPD exacerbations, need for additional treatment, and no improvement in functional parameters, e.g. 6‑min walking test (6MWT), body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV
1
), and as single components.
Results
Treatment ineffectiveness was significantly associated with baseline hemoglobin level, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale and BODE index (
p
= 0.002). Incident exacerbation during the follow-up was associated with baseline bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (
p
< 0.001), and change in treatment with leukocyte count, 6MWT desaturation and fatigue (
p
< 0.001). No improvement in 6MWT was associated with baseline CAT score, body mass index, mMRC, fatigue, 6MWT and BODE index (
p
= 0.002). No improvement in BODE index was associated with leukocyte count, serum interleukin 8 (IL-8) and BALF albumin levels (
p
< 0.001); and no improvement in FEV
1
with CAT score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha) level (
p
< 0.001).
Conclusion
Our results suggest that there is a possibility to identify predictors of short-term tiotropium ineffectiveness in patients with moderate to severe COPD.
Summary
Background
It is well established that anxiety and depression are associated with asthma, but there is limited evidence about the persistence of anxiety/depression in asthma. The aim of our ...study was to assess the long-term predictors of anxiety and depression in adult asthmatic patients.
Methods
A total of 90 adult asthma patients (63 women, age 18–50 years) with different levels of disease control (28 uncontrolled and 34 partially controlled) were assessed at baseline and at follow-up after 7 years for anxiety, depression and asthma control. The same work-up on both occasions included: demographics, living conditions, medical history (e.g. comorbidities, adherence and exacerbations), Hospital Anxiety and Depression Scale (HADS), Asthma Quality of Life Questionnaire (AQLQ), disease control and lung function. Persistence was defined as the HADS scores for anxiety and depression present at baseline and follow-up.
Results
The HADS results at follow-up visit showed 36 (40%) asthma patients with anxiety and 13 (14%) with depression, with the persistence of anxiety in 17 (19%) and of depression in 7 (8%) patients. Significant predictors of anxiety at follow-up were HADS and AQLQ results at baseline and several parameters of asthma control at follow-up (area under the curve AUC 0.917, 95% confidence interval CI 0.829–0.969,
p
< 0.001) and for depression AQLQ mood disorder domain, asthma control and lung function (AUC 0.947, 95% CI 0.870–0.986,
p
< 0.001).
Conclusion
Anxiety and depression persist over years in some patients with asthma. The association between mood disorders and asthma suggests potential mutual treatability.
Epidemiologija i značenje astme Popović Grle, Sanja
Medicus (Zagreb, Croatia : 1992),
05/2013, Letnik:
22, Številka:
1_Astma
Journal Article
Recenzirano
Odprti dostop
Astma je poznata od davnina, ali je tek od polovice prošlog stoljeća izdvojena od ostalih bolesti s teškim disanjem poput srčane ili bubrežne astme te kronične opstruktivne plućne bolesti (KOPB). ...Krajem XX. stoljeća prepoznata je kao važan javnozdravstveni problem, kao uzrok onesposobljenosti, medicinskih troškova i preventabilnih (sprečivih) smrti. Astma je najčešća kronična bolest dječje dobi i među 10 najčešćih bolesti odrasle dobi. Podaci o prevalenciji astme ovisili su o elementima astme koji su istraživani, simptomima, razini provedene dijagnostike, potrošnji lijekova ili dobnoj skupini. Kvalitetna, standardizirana i izjednačena istraživanja o prevalenciji astme (International Study of Asthma and Allergy in Children, ISAAC) posljednjih 15-ak godina pokazuju da se pojavnost astme razlikuje do 20 puta u raznim dijelovima svijeta, od 0,7% u Macau do 18,4% u Škotskoj. Nova istraživanja Svjetske zdravstvene organizacije (SZO) našla su da srednja svjetska prevalencija astme iznosi 4,5%. Rezultati studije ISAAC provedene u više županija Hrvatske pokazuju da pripadamo zemljama s nižom do srednje visokom prevalencijom astme, od 5 do 8% u dobi od 14 godina. Posljednjih desetljeća pratio se porast broja oboljelih od astme, do 50% svakih 10 godina, a nedavna istraživanja pokazuju da je dalji porast prevalencije astme zaustavljen, barem u zemljama s visokom prevalencijom. Prema troškovima zdravstvenog novca smatra se da je astma na 5. mjestu. Mortalitet od astme nije visok (0,23/100.000 stanovnika) i smanjuje se u posljednjih 30-ak godina, ali je većinom mogao biti spriječen. Danas se smatra da je 1 od 250 smrti u svijetu uzrokovana astmom.
Published data indicate that during the last decades there is a possible change in the pattern of sensitization to different aeroallergens in adult population with atopy. The aim of this ...investigation was based on the hypothesis that during last 15 years there has been a change in the structure of prevalence of sensitization to different aeroallergens in adult population of Zagreb and its surroundings with atopy. Medical records from outpatient allergy clinic were screened for the period 1991-2004. We included 794 patients during years 1991-1994, 814 patients during years 1995-1999, and 969 patients during years 2000-2004. Following data were analyzed: age, gender, education level, residence, referral diagnosis, dominant symptoms, results of skin-prick test (SPT), total and specific serum immunoglobulin E. As risk factors for allergic sensitization we determined the decade of birth (p < 0.0001), male gender (p < 0.008), level of education (p < 0.0001), and place of residence (p < 0.05). Proportion of sensitized individuals to pollen significantly increased from the period 1991-1994 towards 2000-2004 (p < 0.001 for the trend) with a significant increase in the proportion of sensitized individuals to weed pollen (p = 0.002 for the trend) while the proportion of sensitized to other two groups of pollen (grasses and trees) was not significantly different. A significant increase in the proportion of sensitized individuals was determined for sensitization to ragweed pollen (p = 0.004 for the trend), and to mugwort (p = 0.005 for the trend). Despite all its limitations primarily based on the selection bias the results of this study are conclusive about the significant change in the proportion of sensitization to different aeroallergens and different pollen groups and individual pollen species during the investigated 15-year time interval.
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