Asthma-chronic obstructive pulmonary disease overlap: Results from a national-multicenter study.

Introduction: Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have a greater disease burden than those with COPD or asthma alone. In this study, it was aimed to determine the prevalence, risk factors, and clinical features of ACO because there are limited national data in Türkiye. Materials and Methods: The study was conducted in a cross-sectional design in nine tertiary-care hospitals. The patients followed with a diagnosis of asthma or COPD for at least one year were enrolled in the study. The frequency of ACO and the characteristics of the patients were evaluated in the asthma and COPD groups. Result: The study included 408 subjects (F/M= 205/203, mean age= 56.24 ± 11.85 years). The overall prevalence of ACO in both groups was 20.8% (n= 85). The frequency was higher in the COPD group than in the asthma group (n= 55; 33.3% vs. n= 22; 9.8%), respectively (p= 0.001). Patients with ACO had similarities to patients with COPD in terms of advanced age, sex, smoking, exposure to biomass during childhood, being born in rural areas, and radiologic features. Characteristics such as a history of childhood asthma and allergic rhinitis, presence of chronic sinusitis, NSAID hypersensitivity, atopy, and high eosinophil counts were similar to those of patients with asthma (p<0.001). The annual decline in FEV1 was more prominent in the ACO group (mean= -250 mL) than in the asthma (mean change= -60 mL) and COPD (mean change= -230 mL) groups (p= 0.003). Conclusions: This study showed that ACO was common among patients with asthma and COPD in tertiary care clinics in our country. ACO should be considered in patients with asthma and COPD who exhibit the abovementioned symptoms.

Hypersensitivity Reactions to Taxanes: A Multicenter Study for Outcomes and Safety of Rapid Drug Desensitization.

PURPOSE: Taxanes can cause hypersensitivity reactions (HSRs), which pose a significant challenge in the treatment of malignancies. Patients who are eligible for rapid drug desensitization (RDD) can continue treatment; however, some patients experience breakthrough reactions (BTRs). Data about risk factors for BTRs during RDDs in patients with HSRs to taxanes are limited. METHODS: This was a multicenter, retrospective study of patients with immediate-HSRs to taxanes. Initial HSRs were classified as grade 1, 2, or 3 based on severity. Prick/intradermal skin tests were performed with implicated taxanes. A 12-step protocol was used during RDD. RESULTS: The study comprised 75 patients (F/M: 63/12, mean age 49.92 ± 11.72 years, 43 HSRs to paclitaxel, 32 HSRs to docetaxel). The majority of reactions (86.7%) occurred during the first or second exposure. The prevalence of drug allergy history was higher in patients with paclitaxel HSR than in those with docetaxel HSR, although it was not statistically significant (23.3% vs. 6.3%). The initial HSRs were mostly grade 2 (n = 50, 66.7%) or grade 3 (n = 22, 29.3%). Skin tests with implicated taxanes were done on 48 patients, and the rate of positive response in patients with grade 1, 2, and 3 initial HSRs were 50%, 17.6%, and 16.7%, respectively. . A total of 255 RDDs were completely performed, although BTRs occurred in 27 (grade 1, 55.6%; grade 2, 40.7%; grade 3, 3.7%). There were no statistically significant correlations between the risk of BTR and age, drug cycle, gender, positivity of skin test or atopy. The step reduction was successfully done on 9 eligible patients with mild or moderate HSRs during the 12-step RDDs. CONCLUSIONS: Our experience demonstrates a 100% success rate in completing the 255 RDDs for taxanes, affirming the safety and efficacy of the RDD within the study population.

Organotypic lung tissue culture as a preclinical model to study host- influenza A viral infection: A case for repurposing of nafamostat mesylate.

Reliable and effective models for recapitulation of host-pathogen interactions are imperative for the discovery of potential therapeutics. Ex vivo models can fulfill these requirements as the multicellular native environment in the tissue is preserved and be utilized for toxicology, vaccine, infection and drug efficacy studies due to the presence of immune cells. Drug repurposing involves the identification of new applications for already approved drugs that are not related to the prime medical indication and emerged as a strategy to cope with slow pace of drug discovery due to high costs and necessary phases to reach the patients. Within the scope of the study, broad-spectrum serine protease inhibitor nafamostat mesylate was repurposed to inhibit influenza A infection and evaluated by a translational ex vivo organotypic model, in which human organ-level responses can be achieved in preclinical safety studies of potential antiviral agents, along with in in vitro lung airway culture. The safe doses were determined as 10 µM for in vitro, whereas 22 µM for ex vivo to be applied for evaluation of host-pathogen interactions, which reduced virus infectivity, increased cell/tissue viability, and protected total protein content by reducing cell death with the inflammatory response. When the gene expression levels of specific pro-inflammatory, anti-inflammatory and cell surface markers involved in antiviral responses were examined, the significant inflammatory response represented by highly elevated mRNA gene expression levels of cytokines and chemokines combined with CDH5 downregulated by 5.1-fold supported the antiviral efficacy of NM and usability of ex vivo model as a preclinical infection model.

Inhaler Steroid Use Changes Oral and Airway Bacterial and Fungal Microbiome Profile in Asthma Patients.

INTRODUCTION: The full spectrum of bacterial and fungal species in adult asthma and the effect of inhaled corticosteroid use is not well described. The aim was to collect mouthwash and induced sputum samples from newly diagnosed asthma patients in the pretreatment period and in chronic asthma patients while undergoing regular maintenance inhaled corticosteroid therapy, in order to demonstrate the bacterial and fungal microbiome profile. METHODS: The study included 28 asthmatic patients on inhaler steroid therapy, 25 steroid-naive asthmatics, and 24 healthy controls. Genomic DNA was isolated from induced sputum and mouthwash samples. Analyses were performed using bacterial primers selected from the 16S rRNA region for the bacterial genome and "panfungal" primers selected from the 5.8S rRNA region for the fungal genome. RESULTS: Dominant genera in mouthwash samples of steroid-naive asthmatics were Neisseria, Haemophilus, and Rothia. The oral microbiota of asthmatic patients on inhaler steroid treatment included Neisseria, Rothia, and Veillonella species. Abundant genera in induced sputum samples of steroid-naive asthma patients were Actinomyces, Granulicatella, Fusobacterium, Peptostreptococcus, and Atopobium. Sputum microbiota of asthma patients taking inhaler steroids were dominated by Prevotella and Porphyromonas. Mucor plumbeus and Malassezia restricta species were abundant in the airways of steroid-naive asthma patients. Choanephora infundibulifera and Malassezia restricta became dominant in asthma patients taking inhaled steroids. CONCLUSION: The oral and airway microbiota consist of different bacterial and fungal communities in healthy and asthmatic patients. Inhaler steroid use may influence the composition of the oral and airway microbiota.

Molecular prevalence of Pneumocystis jirovecii and Cryptosporidium in patients with asthma.

Asthma is characterized by chronic airway inflammation. In addition to allergens, microorganisms can affect the clinical course of asthma. It has been shown that some fungi play an important role in the progression of asthma. However, the effects of Pneumocystis jirovecii and Cryptosporidium spp., on the disease are little known. We investigated P. jirovecii and Cryptosporidium spp. in the sputum and stool sample of patients with asthma (n = 40) by microscopy and PCR compared to the healthy group (n = 40). P. jirovecii (12.5 %), and Cryptosporidium spp. (12.5 %) were detected in the sputum samples of only asthmatic patients (p = 0.029 and 0.029 respectively). However, Crpytosporidium spp. was detected equally in stool samples of both groups (p = 0.682). Our results indicate that P. jirovecii and Cryptosporidium spp. should be considered in patients with asthma and molecular screening of these neglected eukaryotes in respiratory tract samples may be beneficial in the clinical management of the disease.

Impact of a Polymer-Based Nanoparticle with Formoterol Drug as Nanocarrier System In Vitro and in an Experimental Asthmatic Model.

The implementation of nanotechnology in pulmonary delivery systems might result in better and more specific therapy. Therefore, a nano-sized drug carrier should be toxicologically inert and not induce adverse effects. We aimed to investigate the responses of a polymer nano drug carrier, a lysine poly-hydroxyethyl methacrylate nanoparticle (NP) [Lys-p(HEMA)], loaded with formoterol, both in vitro and in vivo in an ovalbumin (OVA) asthma model. The successfully synthesized nanodrug formulation showed an expectedly steady in vitro release profile. There was no sign of in vitro toxicity, and the 16HBE and THP-1 cell lines remained vital after exposure to the nanocarrier, both loaded and unloaded. In an experimental asthma model (Balb/c mice) of ovalbumin sensitization and challenge, the nanocarrier loaded and unloaded with formoterol was tested in a preventive strategy and compared to treatment with the drug in a normal formulation. The airway hyperresponsiveness (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL), both cellular and biochemical, were assessed. The application of formoterol as a regular drug and the unloaded and formoterol-loaded NP in OVA-sensitized mice followed by a saline challenge was not different from the control group. Yet, both the NP formulation and the normal drug application led to a more deteriorated lung function and increased lung inflammation in the OVA-sensitized and -challenged mice, showing that the use of the p(HEMA) nanocarrier loaded with formoterol needs more extensive testing before it can be applied in clinical settings.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis.

Background: An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day-1, 95% CI -5.24-2.62 mg·day-1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.

A drug-responsive multicellular human spheroid model to recapitulate drug-induced pulmonary fibrosis.

Associated with a high mortality rate, pulmonary fibrosis (PF) is the end stage of several interstitial lung diseases. Although many factors are linked to PF progression, initiation of the fibrotic process remains to be studied. Current research focused on generating new strategies to gain a better understanding of the underlying disease mechanism as the animal models remain insufficient to reflect human physiology. Herein, to account complex cellular interactions within the fibrotic tissue, a multicellular spheroid model where human bronchial epithelial cells incorporated with human lung fibroblasts was generated and treated with bleomycin (BLM) to emulate drug-induced PF. Recapitulating the epithelial-interstitial microenvironment, the findings successfully reflected the PF disease, where excessive alpha smooth muscle actin and collagen type I secretion were noted along with the morphological changes in response to BLM. Moreover, increased levels of fibrotic linked COL13A1, MMP2, WNT3 and decreased expression level of CDH1 provide evidence for the model reliability on fibrosis modelling. Subsequent administration of the Food and Drug Administration approved nintedanib and pirfenidone anti-fibrotic drugs proved the drug-responsiveness of the model.

Development of a new needle trap-based method for the determination of some volatile organic compounds in the indoor environment.

Volatile Organic Compounds (VOCs) are a large group of chemicals mostly found in indoor environments such as homes and workplaces. Long term exposure to certain VOCs can cause symptoms in some individuals and therefore, monitoring and controlling air quality can help better manage chronic respiratory diseases. In this study, we aimed to develop an easy-to-use, economical, in house needle trap-based methodology to detect certain VOCs to be used for public and occupational health. For this purpose, a multi-bed (packed with PDMS/Carbopack-X/Carboxen-1000) needle trap device (NTD) was utilized for sampling, enrichment, and injection of the VOCs into the gas chromatography. The performance of the developed method was investigated for the analysis of the group known as BTEX (benzene, toluene, ethylbenzene and xylene). Operational and instrumental parameters such as sampling flow rate and relative humidity, desorption time and temperature were optimized, and the analytical figures of merit of the proposed method have indicated that very low levels of BTEX in air samples can be easily determined by this new method. Overall results have shown that multi-bed NTD offers a high sensitive procedure for sampling and analysis of BTEX in concentration range of 0.002-0.298 mg/m3 in indoor air.

Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.

From inequitable to sustainable e-waste processing for reduction of impact on human health and the environment.

Recycling of electric and electronic waste products (e-waste) which amounted to more than 50 million metric tonnes per year worldwide is a massive and global operation. Unfortunately, an estimated 70-80% of this waste has not been properly managed because the waste went from developed to low-income countries to be dumped into landfills or informally recycled. Such recycling has been carried out either directly on landfill sites or in small, often family-run recycling shops without much regulations or oversights. The process traditionally involved manual dismantling, cleaning with hazardous solvents, burning and melting on open fires, etc., which would generate a variety of toxic substances and exposure/hazards to applicators, family members, proximate residents and the environment. The situation clearly calls for global responsibility to reduce the impact on human health and the environment, especially in developing countries where poor residents have been shouldering the hazardous burden. On the other hand, formal e-waste recycling has been mainly conducted in small scales in industrialized countries. Whether the latter process would impose less risk to populations and environment has not been determined yet. Therefore, the main objectives of this review are: 1. to address current trends and emerging threats of not only informal but also formal e-waste management practices, and 2. to propose adequate measures and interventions. A major recommendation is to conduct independent surveillance of compliance with e-waste trading and processing according to the Basel Ban Amendment. The recycling industry needs to be carefully evaluated by joint effort from international agencies, producing industries and other stakeholders to develop better processes. Subsequent transition to more sustainable and equitable e-waste management solutions should result in more effective use of natural resources, and in prevention of adverse effects on health and the environment.

Outdoor air pollution from industrial chemicals causing new onset of asthma or COPD: a systematic review protocol.

BACKGROUND: Until today, industrial sources contribute to the multifaceted contamination of environmental air. Exposure to air pollutants has the potential to initiate and promote asthma and chronic obstructive pulmonary disease (COPD). At global scale, both entities cause the majority of about 4 million annual deaths by respiratory disease. However, we identified industrial contamination as a subgroup of air pollution that may be associated with this burden and is underinvestigated in research. Therefore, the aim of this study is to investigate associations between substances industrially released into environmental air and the occurrence of asthma and COPD in the human population. Here we present the protocol for our systematic review of the current evidence. METHODS: The following determinations will be applied during the systematic review process and are specified in the protocol that complies with the PRISMA-P statement. Populations of children and adults, as well as outdoor workers, exposed to industrially released air pollutants are of interest. Eligible studies may include subjects as controls who are non- or less exposed to the investigated air pollutants. The outcomes new-onset asthma and/or COPD investigated with risk ratio, odds ratio, hazard ratio, incidence rate ratio, cumulative incidence, and incidence rate are eligible. We will search the electronic literature databases EMBASE, MEDLINE, and Web of Science for peer-reviewed reports of incidence studies and incidence case-control studies. After systematic sorting of initial records, included studies will be subjected to quality assessment. Data will be synthesized qualitatively and, if appropriate, quantitatively for risk ratio and odds ratio. We will maintain and provide a PRISMA report. DISCUSSION: Results of this systematic review may indicate alterations of incidence and risk of asthma and/or COPD in populations within industrial exposure radiuses including outdoor workplaces. Specific causal substances and compositions will be identified, but results will depend on the exposure assessment of the eligible studies. Our approach covers effects of industrial contributions to overall air pollution if studies reportedly attribute investigated emissions to industry. Results of this study may raise the question wether the available higher-level evidence sufficiently covers the current scale of industrial exposure scenarios and their potential harm to respiratory health. TRIAL REGISTRATION: This protocol was registered in PROSPERO, registration number CRD42020151573 .

Is the Perioperative Period No Longer a Problem for Adult Asthmatics under Control?-OPERA Study.

OBJECTIVES: Asthma is a global problem and chronic condition that persists through patient's entire life, during which the possibility of a surgical procedure is common. An accurate clinical and functional evaluation of respiratory functions and asthma control is needed in patients undergoing surgical procedures and requiring general anesthesia. The aim of this study was to disclose any possible relation between postoperative complications and some pre- and postoperative factors. MATERIALS AND METHODS: In this prospective cross-sectional study, randomly selected 111 asthmatic patients who presented to 10 different tertiary centers were included. The patients were evaluated at three different periods; any day between 1-7 days before surgery, and postoperative third and seventh to tenth days. RESULTS: Among the patients included in the study, 86 (77.5%) were women and mean age was 52.2±13.8 years. General anesthesia was the most common anesthesia type (89.2%), and 33.3% of patients had had a thoracoabdominal surgery. There was a statistically significant difference between pre- and postoperative third-day values, including ACT scores (22.2±3.16 and 21.59±3.84, respectively; p<0.001); forced expiratory volume during the first second (84.92±19.12 and 78.26±18.47, respectively; p<0.001); peak flow rate (79.51±21.12 and 70.01±19.72, respectively; p<0.001); and SaO2 (96.95±1.82 and 95.8±3.32, respectively; p<0.001). Bronchospasm and pain were the most common complications during the postoperative period. CONCLUSION: Controlled asthma under treatment steps 1-2-3 does not cause any serious postoperative pulmonary complications (PPCs). Therefore, achieving an optimal control level of asthma during the preoperative period must be considered the "gold standard" to reduce the risk of PPCs in asthmatic patients.

Validity and Reliability of the Assessment Tool for Asthma (ATA) Questionnaire: the ATA Study.

OBJECTIVES: A multicenter trial was designed to validate the "Assessment Tools for Asthma (ATA)" questionnaire, a newly developed questionnaire, which evaluates both asthma control and risk factors associated with asthma control with a single instrument. MATERIALS AND METHODS: This cross-sectional study involved 810 cases from 14 clinics in 9 Turkish cities. The ATA questionnaire and Asthma Control Test (ACT) were administered. The Visual Analog Scale (VAS) was used to evaluate the control status of 100 randomized cases. ATA is an eight-item physician-administered questionnaire. It comprises the following two sections-ATA1, assesses symptomatic control criteria, and the remaining section, queries the flare-up of asthma, control of comorbidities, treatment adherence, and inhaler technique. RESULTS: The mean scores for ATA1, ATA total, VAS, and ACT were 24.7±14.8, 53.8±19, 7.1±3, and 18.8±5.5, respectively. According to the ATA questionnaire, among all patients, 34.3% had controlled, 18.8% had partly controlled, and 46.9% had uncontrolled asthma. Furthermore, 16.6% patients had flare-ups between visits, 96.4% patients had uncontrolled comorbidity, 17% patients had irregular asthma treatment, and only 8.4% patients used the incorrect inhaler technique. The ATA questionnaire showed internal consistency (Cronbach's alpha coefficient=0.683). ACT, ATA1, and two specialists' evaluations using VAS correlated strongly with the ATA total scores (Spearman correlation coefficient (r) values: 0.776, 0.783, and 0.909, respectively; p-values: p<0.001, p<0.001, and p<0.001, respectively). According to Receiver Operating Characteristic analysis, the cut-off value of ATA was 50 (sensitivity=84.4%, specificity=82.40%). CONCLUSION: The validated ATA questionnaire may be a practical tool for physicians in asthma management.

Exhaled Breath Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review.

Malignant pleural mesothelioma (MPM) is mainly related to previous asbestos exposure. There is still dearth of information on non-invasive biomarkers to detect MPM at early stages. Human studies on exhaled breath biomarkers of cancer and asbestos-related diseases show encouraging results. The aim of this systematic review was to provide an overview on the current knowledge about exhaled breath analysis in MPM diagnosis. A systematic review was conducted on MEDLINE (PubMed), EMBASE and Web of Science databases to identify relevant studies. Quality assessment was done by the Newcastle-Ottawa Scale. Six studies were identified, all of which showed fair quality and explored volatile organic compounds (VOC) based breath profile using Gas Chromatography Coupled to Mass Spectrometry (GC-MS), Ion Mobility Spectrometry Coupled to Multi-capillary Columns (IMS-MCC) or pattern-recognition technologies. Sample sizes varied between 39 and 330. Some compounds (i.e, cyclohexane, P3, P5, P50, P71, diethyl ether, limonene, nonanal, VOC IK 1287) that can be indicative of MPM development in asbestos exposed population were identified with high diagnostic accuracy rates. E-nose studies reported breathprints being able to distinguish MPM from asbestos exposed individuals with high sensitivity and a negative predictive value. Small sample sizes and methodological diversities among studies limit the translation of results into clinical practice. More prospective studies with standardized methodologies should be conducted on larger populations.

Concordance in molecular genetic analysis of tumour tissue, plasma, and exhaled breath condensate samples from lung cancer patients.

AIM: Lung adenocarcinoma is characterized by poor prognosis and short survival rates. Therefore, tools to identify the tumoural molecular structure and guide effective diagnosis and therapy decisions are essential. Surgical biopsies are highly invasive and not conducive for patient follow-up. To better understand disease prognosis, novel non-invasive analytic methods are needed. The aim of the present study is to identify the genetic mutations in formalin-fixed paraffin-embedded (FFPE) tissue, plasma, and exhaled breath condensate (EBC) samples by next-generation sequencing and evaluate their utility in the diagnosis and follow-up of patients with lung adenocarcinoma. METHOD: FFPE, plasma, and EBC samples were collected from 12 lung adenocarcinoma patients before treatment. DNA was extracted from the specimens using an Invitrogen PureLink Genomic DNA Kit according to the manufacturer's instructions. Amplicon-based sequencing was performed using Ion AmpliSeq Colon and Lung Cancer Research Panel v2. RESULTS: Genetic alterations were detected in all FFPE, plasma, and EBC specimens. The mutations in PIK3CA, MET, PTEN, SMAD4, and FGFR2 genes were highly correlated in six patients. Somatic and novel mutations detected in tissue and EBC samples were highly correlated in one additional patient. The EGFR p.L858R and KRAS p.G12C driver mutations were found in both the FFPE tissue specimens and the corresponding EBC samples of the lung adenocarcinoma patients. CONCLUSION: The driver mutations were detected in EBC samples from lung adenocarcinoma patients. The analysis of EBC samples represents a promising non-invasive method to detect mutations in lung cancer and guide diagnosis and follow-up.

"Whole" vs. "fragmented" approach to EAACI pollen season definitions: A multicenter study in six Southern European cities.

BACKGROUND: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. OBJECTIVE: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. METHODS: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. RESULTS: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). CONCLUSION: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.

Immunological methods for diagnosis and monitoring of IgE-mediated allergy caused by industrial sensitizing agents (IMExAllergy).

Industrial sensitizing agents (allergens) in living and working environments play an important role in eliciting type 1 allergic disorders including asthma and allergic rhinitis. Successful management of allergic diseases necessitates identifying their specific causes (ie, identify the causative agent(s) and the route of contact to allergen: airborne, or skin contact) to avoid further exposure. Identification of sensitization by a sensitive and validated measurement of specific IgE is an important step in the diagnosis. However, only a limited number of environmental and occupational allergens are available on the market for use in sIgE testing. Accordingly, specific in-house testing by individual diagnostic and laboratory centers is often required. Currently, different immunological tests are in use at various diagnostic centers that often produce considerably divergent results, mostly due to lack of standardized allergen preparation and standardized procedures as well as inadequate quality control. Our review and meta-analysis exhibited satisfactory performance of sIgE detection test for most high molecular weight (HMW) allergens with a pooled sensitivity of 0.74 and specificity of 0.71. However, for low molecular weight (LMW) allergens, pooled sensitivity is generally lower (0.28) and specificity higher (0.89) than for HMW tests. Major recommendations based on the presented data include diagnostic use of sIgE to HMW allergens. A negative sIgE result for LMW agents does not exclude sensitization. In addition, the requirements for full transparency of the content of allergen preparations with details on standardization and quality control are underlined. Development of standard operating procedures for in-house sIgE assays, and clinical validation, centralized quality control and audits are emphasized. There is also a need for specialized laboratories to provide a custom service for the development of tests for the measurement of putative novel occupational allergens that are not commercially available.