Objective: The large amount of evidence and the renewed interest in upper and lower airways involvement in infectious and inflammatory diseases has led Interasma (Global Asthma Association) to take a ...position on United Airways Diseases (UAD).Methods: Starting from an extensive literature review, Interasma executive committee discussed and approved this Manifesto developed by Interasma scientific network (INES) members.Results: The manifesto describes the evidence gathered to date and defines, states, advocates, and proposes issues on UAD (rhinitis, rhinosinusitis and nasal polyposis), and concomitant/comorbid lower airways disorders (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnoea) with the aim of challenging assumptions, fostering commitment, and bringing about change. UAD refers to clinical pictures characterized by the coexistence of upper and lower airways involvement, driven by a common pathophysiological mechanism, leading to a greater burden on patient's health status and requiring an integrated diagnostic and therapeutic plan. The high prevalence of UAD must be taken into account. Upper and lower airways diseases influence disease control and patient's quality of life.Conclusions: Patients with UAD need to have a timely and adequate diagnosis, treatment, and, when recommended, referral for management in a specialized center. Diagnostic testing including skin prick or serum specific IgE, lung function, fractional exhaled nitric oxide (FeNO), polysomnography, allergen-specific immunotherapies, biological therapies and home based continuous positive airway pressure (CPAP) whenever these are recommended, should be part of the management plan for UAD. Education of medical students, physicians, health professionals, patients and caregivers on the UAD is needed.
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.
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.
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.
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.
Beta-blockers in asthma: myth and reality Tiotiu, Angelica; Novakova, Plamena; Kowal, Krzysztof ...
Expert review of respiratory medicine,
09/2019, Letnik:
13, Številka:
9
Journal Article
Recenzirano
Introduction: Patients with asthma often have important co-morbidities which reduce the likelihood of gaining optimal asthma control. Beta2-blockers are commonly prescribed for the treatment of ...different clinical indications, including coronary artery disease, cardiac arrhythmia, arterial hypertension, heart failure and glaucoma.
Areas covered: The aim of this reviw is to summarize current evidence on the effect of systemic and local β-blockers on asthma outcomes based on their pharmacologic properties,and to help clinicians when prescribing for patients with asthma and co-morbidities. Current data suggest that risk of asthma worsening from systemic and local use of non-selective β-blockers outweighs any potential benefits for their clinical indications. Recent studies confirm that topical and systemic prescription of cardio-selective β-blockers is not associated with a significant increased risk of moderate or severe asthma exacerbations.
Expert opinion: Non-selective β-blockers should not be prescribed for the management of comorbidities in patients with asthma while cardio-selective β-blockers, preferably in low doses, may be used when strongly indicated and other therapeutic options are not available. More prospective real-life studies are needed to evaluate the risk of long-term use of β-blockers in patients with asthma.
The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leukotrienes (LTs), which are important mediators of inflammation and connective tissue remodelling. The aim of ...this study was to evaluate if single nucleotide polymorphisms (SNPs) of ALOX5AP confer risk of SSc and/or SSc-related organ involvement.
Seven SNPs of ALOX5AP (rs17222814, rs17216473, rs10507391, rs4769874, rs9551963, rs9315050 and rs7222842) were genotyped in a cohort of 977 patients with SSc and 558 healthy controls from centres collaborating within the European Scleroderma Trials and Research group. In 22 SSc patients, concentrations of cysteinyl LTs and LT B4 (LTB4) were measured in the supernatants of ionophore-stimulated peripheral blood mononuclear cells (PBMCs) by means of commercially available enzyme immunoassay kits.
Significant association was found between rs10507391 polymorphism (T/A) of ALOX5AP and the risk of SSc odds ratio (OR) 1.27 (95% CI 1.07, 1.50), P < 0.05 vs controls, the presence of SSc-related interstitial lung disease on high-resolution CT of the lungs OR 1.45 (95% CI 1.17, 1.79), P < 0.05 vs patients without SSc-related interstitial lung disease as well as with restrictive ventilatory defect forced vital capacity <70% of predicted; OR 1.51 (95% CI 1.16, 1.97), P < 0.05 vs SSc patients without pulmonary restriction. PBMCs from SSc carriers of rs10507391 allele A synthesized greater amounts of cysteinyl LTs as compared with SSc patients with rs10507391 TT genotype ( P < 0.05). Synthesis of LTB4 did not differ significantly between the two groups.
The results of our study indicate that the genetic variants of ALOX5AP might play a role in the development of SSc-related pulmonary fibrosis.
The aim of this study was to determine molecular defects in mitochondrial DNA (mtDNA) with the use of large‐scale genome analysis in malignant canine mammary gland tumours and indicate whether these ...changes were linked with the carcinogenesis process. With the use of the NGS technology, we sequenced 27 samples of mtDNA isolated from blood and tumours obtained from 13 dogs with mammary gland tumours. The total number of mutations and polymorphisms in the analysed mitochondrial genomes was 557. We identified 383 single nucleotide polymorphisms (SNP), 32 indels (or length polymorphisms), 4 mutations, 137 heteroplasmic positions and 1 indel mutation. The highest variability (132 changes) was observed in the variable number of tandem repeats (VNTR) region. The heteroplasmy rate in VNTR varied among individuals and even between two tumours in one organism. Our previous study resulted in determination of a probable CpG island in this region, thus it is not excluded that these changes might alter mtDNA methylation. Only the ATP8 gene was not affected by any polymorphisms or mutations, whereas the COX1 gene had the highest number of polymorphisms from all protein‐coding genes. One change m.13594G>A was detected in a region spanning two genes: ND5 and ND6, from which a deleterious effect was observed for the ND5 protein. Molecular changes were frequently observed in the TΨC loop, which is thought to interact with ribosomal RNA.
•Inflammation is involved in the pathogenesis of pulmonary arterial hypertension (PAH).•PAH patients present elevated sCD163 and lower serum sTWEAK levels than controls.•The sTWEAK/sCD163 ratio ...appears to be a better indicator of the severity of PAH than either marker alone.•The exact role of sCD163 or CD163–sTWEAK interaction in PAH remains to be established.
Inflammation may play a pivotal role in the pathogenesis of pulmonary arterial hypertension (PAH). We evaluated the concentrations of serum sTWEAK, its scavenger receptor sCD163 and sTWEAK/sCD163 ratio in patients with PAH.
The study enrolled 26 stable patients with PAH confirmed by right heart catheterization and 24 healthy volunteers matched for age, sex and body weight. All patients underwent transthoracic echocardiography, cardiopulmonary exercise test, 6-min walk test, measurement of lung diffusing capacity for the carbon monoxide (DLCO) and venous blood tests. Concentrations of sTWEAK and sCD163 were determined using ELISA kits.
The PAH patients were characterized by significantly higher median serum sCD163 levels (1072 vs 890ng/ml, p=0.04) together with lower serum sTWEAK concentrations (200 vs 278.1pg/ml, p=0.003) comparing to control subjects. sTWEAK/sCD163 ratio was therefore significantly lower in PAH group (0.18 vs 0.33, p=0.0005). No correlation was found between sTWEAK and sCD163 concentrations in both groups. We observed statistically significant inverse correlation between peak VO2 consumption and sCD163 concentrations (r=−0.52, p<0.05) and positive with sTWEAK/sCD163 ratio (r=0.45, p<0.05) in PAH group. Moreover, sTWEAK/sCD163 ratio positively correlated with % of predicted values of DLCO (r=0.42, p<0.05).
Patients with PAH present altered serum sTWEAK and sCD163 levels. The sTWEAK/sCD163 ratio appears to be a better indicator of the severity of PAH as compared to sTWEAK or sCD163 alone. The exact role of sCD163 or interaction between CD163 and sTWEAK in the initiation or progression of PAH as well as their potential prognostic significance remains to be established.
Introduction
Fibrosis is one of the factors contributing to the development of primary acquired lacrimal duct obstruction (LDO). LIGHT (homologous to lymphotoxins, exhibiting inducible expression and ...competing with herpes simplex virus glycoprotein D for herpes virus entry mediator HVEM), a receptor expressed by T lymphocytes, has recently emerged as a new regulator of connective tissue remodeling and fibrotic response. The purpose of this study was to evaluate the role of LIGHT in the pathogenesis of LDO through: (1) assessment of expression of LIGHT and its two receptors, HVEM and LTβR (lymphotoxin β receptor), and (2) investigation of potential relationships between expression of LIGHT and its receptors and clinical and histopathologic features.
Methods
Lacrimal sacs of 30 patients undergoing endoscopic dacryocystorhinostomy because of LDO were assessed intraoperatively and histopathologically with respect to inflammation and fibrosis. Expression of LIGHT, HVEM and LTβR was assessed by immunohistochemistry using specific antibodies and evaluated semiquantitatively using a four-grade scoring system.
Results
All investigated molecules, LIGHT/TNFSF14, HVEM and LTβR, were expressed in biopsies from all patients. The most prominent expression was seen within inflammatory infiltrates. Expression of LIGH, HVEM and LTβR correlated significantly with the intensity of fibrosis and duration of the disease. In multivariate analysis only LIGHT showed a significant relationship with fibrosis (
β
coefficient = 0.759,
p
= 0.02). There was no significant correlation between expression of any molecule and other demographic or clinical features.
Conclusion
We assume that LIGHT along with its receptors may be a factor contributing to fibrosis and synechiae formation in the lacrimal sac. This assumption needs to be proven in a future study in a group of patients who fail to improve after the first operation.
Airway hyperresponsiveness (AHR) is a cardinal feature of asthma. Asthma is a heterogenous disorder which consists of different phenotypes and endotypes. Mechanisms leading to AHR may differ in ...different asthma subtypes. Allergy to perennial allergens, including house dust mites (HDM) is a major risk factor for asthma development. The aim of this study was to determine predictors of AHR in a well-characterized population of HDM-allergic patients.
In a retrospective analysis 843 patients with HDM-allergic rhinitis with/without asthma were evaluated. The following parameters were included in the analysis: serum concentration of total (t)- and Dermatophagoides pteronyssinus (Dp)-specific IgE, fractional exhaled nitric oxide concentration (FeNO), lung function tests, bronchial challenge with histamine, age sex, and body mass index (BMI). Linear regression analysis was used to determine predictors of AHR.
In a simple linear regression analysis baseline lung function results expressed as either forced expiratory volume in 1 s (FEV1) or maximal expiratory flow at 50% of the forced vital capacity (MEF50), FeNO, tIgE, DpIgE, age and BMI affected AHR. A multiple regression analysis demonstrated that in the whole group of HDM-allergic patients the most important, independent predictors of AHR were MEF50, FeNO and DpIgE.
Even in a well-characterized asthma phenotype several processes participate in development of AHR. Major, independent predictors of AHR: lung function parameters, FeNO and DpIgE indicate possible targets for therapeutic intervention in a population of HDM-allergic patients.
Background. Bronchial asthma (A) is frequently diagnosed in patients with chronic cough. The study was conducted to determine whether an evaluation of fractional exhaled nitric oxide (FeNO) ...concentration can be used as a screening test for asthma in young adults with chronic cough (CCP). Methods. The study was performed on 540 (mean age 26.5; range 18-45 years), nonsmoking young CCP. All patients had resting spirometry within normal limits and no abnormalities on chest radiographs. Skin prick tests with common aeroallergens, bronchial provocation challenge with histamine, and evaluation of FeNO concentration were performed in all patients. One hundred healthy, nonsmoking, nonatopic subjects were used as control subjects (HC). Results. Asthma (A) was diagnosed in 178 CCP (32.96%). Other frequent diagnoses included rhinitis/sinusitis (R) and gastroesophageal reflux (GERD). The median FeNO concentration in A (86 ppb; 95% CI 72 to 94,5 ppb) was significantly greater than in R (37 ppb; 95% CI 35,6 to 42,9 ppb; p < 0.0001), GERD (14,8 ppb; 95%CI 13.3 to 16.2 ppb; p < 0.0001), or in HC (13 ppb; 95%CI 11 to 15 ppb; p < 0.0001). Significant correlation was found between logFeNO and bronchial reactivity expressed as logPC20 (r = −0.529; 95%CI −0.616 to −0.429; p < 0.0001), but even stronger correlation was demonstrated between logFeNO and peripheral blood eosinophilia (r = 0.757; 95%CI 0.717 to 0.792). Receiver Operator Characteristic (ROC) curve analysis revealed that CCP can be screened for A by measuring FeNO concentration. Using 40 ppb as a cut-off value for the FeNO concentration, the specificity 82.6% and sensitivity 88.3% can be achieved. Conclusion. In clinical practice, assessment of FeNO concentration can be used as a screening test for asthma in young adults who have chronic cough.
Methods ELISA and inhibition ELISA with recombinant birch, mugwort and ragweed profilins and their methylated counterparts were performed using sera from allergic rhinitis patients.
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