Venom Immunotherapy Does Not Affect Survival of Patients with Malignant Tumor in Poland.

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients' survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace's crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace's cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.

Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study.

RATIONALE: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. OBJECTIVES: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. METHODS: In this cross-sectional study, we assessed real-world data using the MASK-air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma. MEASUREMENT AND MAIN RESULTS: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma. CONCLUSIONS: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Asthma and rhinitis control in adolescents and young adults: A real-world MASK-air study.

BACKGROUND: In allergic rhinitis and asthma, adolescents and young adult patients are likely to differ from older patients. We compared adolescents, young adults and adults on symptoms, control levels, and medication adherence. METHODS: In a cross-sectional study (2015-2022), we assessed European users of the MASK-air mHealth app of three age groups: adolescents (13-18 years), young adults (18-26 years), and adults (>26 years). We compared them on their reported rhinitis and asthma symptoms, use and adherence to rhinitis and asthma treatment and app adherence. Allergy symptoms and control were assessed by means of visual analogue scales (VASs) on rhinitis or asthma, the combined symptom-medication score (CSMS), and the electronic daily control score for asthma (e-DASTHMA). We built multivariable regression models to compare symptoms or medication accounting for potential differences in demographic characteristics and baseline severity. RESULTS: We assessed 965 adolescent users (15,252 days), 4595 young adults (58,161 days), and 15,154 adult users (258,796 days). Users of all three age groups displayed similar app adherence. In multivariable models, age groups were not found to significantly differ in their adherence to rhinitis or asthma medication. These models also found that adolescents reported lower VAS on global allergy, ocular, and asthma symptoms (as well as lower CSMS) than young adults and adults. CONCLUSIONS: Adolescents reported a better rhinitis and asthma control than young adults and adults, even though similar medication adherence levels were observed across age groups. These results pave the way for future studies on understanding how adolescents control their allergic diseases.

The Effect of the Surface Topography of High-Speed Steel Cutting Blades Made Using Various Methods on Their Technological and Functional Properties.

Indication of the proper scope of application of high-speed steels (HSS) produced by conventional methods and powder metallurgy for cutting tool blades requires a thorough assessment of their properties in various cutting conditions. According to common knowledge, the properties of tools made of both types of steel are largely determined by the arrangement of carbide phases. It turns out, however, that the surface morphology of the cutting blades is at least as important for their operational properties. This was already indicated by the preliminary research of the authors of the article, in which it was found that the surface topography significantly affects their durability depending on the applied value of the cutting speed in dry machining conditions and in the presence of a cooling lubricant. As it turned out, contrary to the literature data, blades made of sintered HSS do not have better service properties in all cutting conditions than blades made by conventional methods (e.g., in forging and hot rolling processes). Hence, it was necessary to determine the justified range of use of both types of steel for cutting blades. Cutting blades with a similar chemical composition from conventional high-speed steel and those produced in the powder metallurgy process were tested. Wear curves were determined on the basis of the tests. On this basis, for the assumed value of the blunting index, the tool life of the cutting edges was determined during the cutting of selected structural steel, commonly used for high-strength machine parts. Tests of the cutting ability of the blades were carried out without and with the use of a cooling--lubricating liquid. In order to correctly interpret the obtained results of the wear and durability tests of the cutting edges, verification tests were carried out. A detailed analysis of the research material made it possible to determine the recommended range of applicability of conventional and sintered HSS for the tested case.

Impairment of EQ-5D-5L Domains According to Allergic Rhinitis and Asthma Control: A MASK-air Real-World Study.

BACKGROUND: EQ-5D-5L (EuroQOL, 5 Domains, 5 Levels) is a widely used health-related quality-of-life instrument, comprising 5 domains. However, it is not known how each domain is impacted by rhinitis or asthma control. OBJECTIVE: To assess the association between rhinitis or asthma control and the different EQ-5D-5L domains using data from the MASK-air mHealth app. METHODS: In this cross-sectional study, we assessed data from all MASK-air users (2015-2021; 24 countries). For the levels of each EQ-5D-5L domain, we assessed rhinitis and asthma visual analog scales (VASs) and the combined symptom-medication score (CSMS). We built ordinal multivariable models assessing the adjusted association between VAS/CSMS values and the levels of each EQ-5D-5L domain. Finally, we compared EQ-5D-5L data from users with rhinitis and self-reported asthma with data from users with rhinitis alone. RESULTS: We assessed 5354 days from 3092 users. We observed an association between worse control of rhinitis or asthma (higher VASs and CSMS) and worse EQ-5D-5L levels. In multivariable models, all VASs and the CSMS were associated with higher levels of pain/discomfort and daily activities. For anxiety/depression, the association was mostly observed for rhinitis-related tools (VAS nose, VAS global, and CSMS), although the presence of self-reported asthma was also associated with worse anxiety/depression. Worse mobility ("walking around") was particularly associated with VAS asthma and with the presence of asthma. CONCLUSIONS: A worse rhinitis control and a worse asthma control are associated with higher EQ-5D-5L levels, particularly regarding pain/discomfort and activity impairment. Worse rhinitis control is associated with worse anxiety/depression, and poor asthma control with worse mobility.

UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan.

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.

Biologicals in the treatment of chronic rhinosinusitis with nasal polyps ­ position of the Polish Society of Otorhinolaryngologists ­Head and Neck Surgeons and the Polish Society of Allergology experts

Chronic rhinosinusitis with nasal polyps (CRSwNP) has a significant impact on the well-being and social functions of the patient. The generalized inflammatory process with the formation of nasal polyps and excess eosinophils in the mucosa of the paranasal sinuses is called type 2 inflammation, which is mediated by Th2 lymphocytes ­ cells of the immune system responsible for chronic inflammatory processes. Today, we also know the key pro-inflammatory mediators against which new drugs have been developed, the so-called biological drugs, are produced in cell lines. In this document, we present currently available biologicals approved for the treatment of patients with T2-related chronic rhinosinusitis.

Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

Development and validation of an electronic daily control score for asthma (e-DASTHMA): a real-world direct patient data study.

BACKGROUND: Validated questionnaires are used to assess asthma control over the past 1-4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA). METHODS: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16-90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test-retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician. FINDINGS: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68-0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59-0·68). They also displayed high test-retest reliability (intraclass correlation coefficients range 0·79-0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69-0·79; effect size measures range 0·57-0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61-0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68-0·78). INTERPRETATION: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation. FUNDING: None.

Clinical profiles of patients referred for biological therapy and major limitations in the qualification paths in a specialist asthma centre.

Introduction: Despite the proven efficacy of biologics in the treatment of severe asthma, still a limited number of patients are included in the Polish therapeutic programme. Aim: To identify major limitations in the qualification paths and predominant reasons leading to exclusion from available biologic treatments. The clinical profiles of patients referred for biologics were also examined. Material and methods: Data on demographic characteristics, clinical profile, biomarkers, and medical history from one visit of patients that had been referred for qualification for biologics in 2018/2019 to the Barlicki Hospital (Poland) were collected. A comparison between eligible and ineligible patients was made. Results: Within 2 years, only 116 patients had been referred to the biologic therapy of whom 93 (80%) had been suitable for the biologic programme. Criteria for the omalizumab programme included major limitations such as: frequent use of oral corticosteroids in the past, and serum total-IgE 30-1000 IU/ml, and for mepolizumab were blood eosinophil count (EOScount) > 350/µl and spirometric criterion. Ineligible patients had a significantly lower EOScount and better lung function than eligible individuals despite no significant differences in the number of exacerbations or quality of life between groups. A high percentage of ineligible patients had been referred to re-verify the diagnosis of severe asthma. Conclusions: Potential limitations for biologic therapy include restrictive criteria limiting the group of patients to the most severe cases and referring patients with difficult-to-treat asthma without a differential diagnosis. Low awareness and knowledge among physicians who often are not familiar with qualification criteria require extensive education.

Digitally-enabled, patient-centred care in rhinitis and asthma multimorbidity: The ARIA-MASK-air® approach.

MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma.

Predictors of excessive short-acting ß2-agonist use and asthma exacerbations: a retrospective analysis of a Polish prescription database.

Introduction: Despite being linked to unfavourable outcomes, short-acting ß2-agonists (SABAs) are still overused by a substantial proportion of patients with asthma. Aim: To analyse the prevalence and predictors of SABA overuse and exacerbations in patients with asthma in a nationwide database of prescription purchase records. Material and methods: The prevalence of excessive SABA use (≥ 12 canisters) and overuse (≥ 3 canisters) was analysed among patients aged 18-64 years who purchased asthma medications in 2018. Predictors of excessive SABA use and SABA overuse were examined by quasi-Poisson regression. Negative binomial regression was used to study the association of excessive SABA use or overuse to the risk of asthma exacerbation defined as a prescription for oral corticosteroids. Results: Of 91,763 patients with asthma, 42,189 (46%) were SABA users (mean age, 47 years; 58% female). Among them, 34% purchased ≥ 3 SABA canisters, and 6% purchased ≥ 12 canisters. The risk (risk ratio, 95% CI) of excessive SABA use was lower in patients with concomitant prescriptions for inhaled corticosteroids (0.41, 0.34-0.48) or inhaled corticosteroids and long-acting ß2-agonists (0.52, 0.47-0.56), women (0.63, 0.58-0.68), and those in secondary care (0.60, 0.44-0.66); older age was associated with a higher risk of excessive SABA use (1.06, 1.03-1.10). Excessive SABA use was the strongest predictor of asthma exacerbations among all patients (3.24, 2.84-3.70) and in those with ≥ 1 exacerbation (1.60, 1.50-1.71). Conclusions: Excessive SABA use is highly prevalent in asthma management, is associated with lack of prescriptions for inhaled corticosteroids, and substantially increases the exacerbation risk.

Monoclonal antibodies in the management of asthma: Dead ends, current status and future perspectives.

Patients with moderate-to-severe asthma may now be treated using a variety of monoclonal antibodies that target key inflammatory cytokines involved in disease pathogenesis. Existing clinical data on anti-IgE, anti-IL-5 and other immunological pathways indicate these therapies to offer reduced exacerbation rates, improved lung function, greater asthma control and better quality of life. However, as several patients still do not achieve satisfactory clinical response with the antibodies available, many more biologics, aiming different immunological pathways, are under evaluation. This review summarizes recent data on existing and potential monoclonal antibodies in asthma. Recent advances have resulted in the registration of a new antibody targeting TSLP (tezepelumab), with others being under development. Some of the researched monoclonal antibodies (e.g. anti-IL-13 tralokinumab and lebrikizumab or anti-IL-17A secukinumab) have shown optimistic results in preliminary research; however, these have been discontinued in asthma clinical research. In addition, as available monoclonal antibody treatments have shown little benefit among patients with T2-low asthma, research continues in this area, with several antibodies in development. This article summarizes the available pre-clinical and clinical data on new and emerging drugs for treating severe asthma, discusses discontinued treatments and outlines future directions in this area.

Effect of Laser Heating on the Life of Cutting Tools Coated with Single- and Multilayer Coatings Containing a TiN Layer.

This study proposes a novel use of laser heating to increase the adhesion between coatings fabricated by low-temperature PVD and replaceable cemented carbide cutting inserts, thus extending the life of these cutting tools in the machining of difficult-to-machine materials. Our previous studies conducted on CVD coatings showed that these coatings had higher adhesion due to a much higher process temperature. However, taking into account the fact that PVD coatings have better technological properties (e.g., lower structure porosity, higher hardness, and better tribological properties) than CVD coatings, it is fully justified to investigate ways of improving the PVD coating adhesion to the substrate. In this study, replaceable cutting inserts with different hard coatings of titanium nitride were used. Laser heating was conducted with different power densities. The adhesion strength of the tested coatings was determined via vibration spectrum analysis. In addition, 2D surface imaging, scanning electron microscopy, and X-ray fluorescence spectrometry were employed to examine the coatings after laser heating. A significant increase in the adhesion of single-layer (TiN) and double-layer (TiCN + TiN) coatings to the cemented carbide substrate, together with increased tool life, was observed after heating the samples with 40% of the maximum laser power. The application of a multilayer coating containing thermal shock-sensitive (TiAlSi) N did not increase the tool life. This paper attempts to interpret the obtained results.

Short-Acting Beta-2-Agonist Exposure and Severe Asthma Exacerbations: SABINA Findings From Europe and North America.

BACKGROUND: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists. OBJECTIVE: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe. METHODS: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations. RESULTS: Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications. CONCLUSIONS: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation.

RATIONALE: Asthma phenotyping requires novel biomarker discovery. OBJECTIVES: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). METHODS: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. RESULTS: In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-ß and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. CONCLUSIONS: The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.

Improving the risk-to-benefit ratio of inhaled corticosteroids through delivery and dose: current progress and future directions.

INTRODUCTION: Inhaled corticosteroids (ICS) are known to increase the risk of systemic and local adverse effects, especially with high doses and long-term use. Hence, considerable resources are invested to improve pharmacokinetic/pharmacodynamic (PK/PD) properties of ICS, effective delivery systems and novel combination therapies to enhance the risk-to-benefit ratio of ICS. AREAS COVERED: There is an unmet need for new solutions to achieve optimal clinical outcomes with minimal dose of ICS. This paper gives an overview of novel treatment strategies regarding the safety of ICS therapy on the basis of the three most recent molecules introduced to our everyday clinical practice - ciclesonide, mometasone furoate, and fluticasone furoate. Advances in aerosol devices and new areas of inhalation therapy are also discussed. EXPERT OPINION: Current progress in improving the risk-to-benefit ratio of ICS through dose and delivery probably established pathways for further developments. This applies both to the improvement of the PK/PD properties of ICS molecules but also includes technical aspects that lead to simplified applicability of the device with simultaneous optimal drug deposition in the lungs. Indubitably, the future of medicine lies not only in the development of new molecules but also in technology and digital revolution.

Impact of inhalers used in the treatment of respiratory diseases on global warming.

The term "carbon footprint" describes the emission of greenhouse gases into the environment as a result of human activities. The healthcare sector is responsible for 5-8% of the value of global greenhouse gas emissions, of which medical aerosols account for only 0.03% of the total emissions. The reduction of greenhouse gases, including those used for the production and use of medicinal products and medical devices, is part of the responsibilities that Poland and the respective countries should undertake in order to implement the assumptions of international law. At the level of medical law, this obligation correlates with the need to exercise due diligence in the process of providing health services, including the selection of low-emission medical products and devices (inhalers) and providing patients with information on how to handle used products and devices, with particular emphasis on those that imply greenhouse gas emissions. Pressurized metered dose inhalers (pMDI) containing the hydrofluoroalkane 134a demonstrate the largest carbon footprint, followed by a metered dose liquid inhaler and dry powder inhalers (DPI). The carbon footprint of DPI with a given drug is 13-32 times lower than it is in the case of the corresponding pMDI. Replacement of pMDI by DPI is one of the effective methods to reduce the carbon footprint of inhalers, and the replacement should be based on current medical knowledge. A recycling system for all types of inhalers must be urgently implemented.

Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation.

BACKGROUND: In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. OBJECTIVE: We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics. METHODS: We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort. RESULTS: Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin). CONCLUSION: FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.