Asthma

This study is designed to assess the validity and reliability of the Turkish version of the Brompton Breathing Pattern Assessment Tool (BPAT). BPAT is a well-established tool used to assess the breathing patterns of individuals with respiratory conditions. In this study, a group of asthma patients will be evaluated using the BPAT to determine its applicability and consistency in the Turkish-speaking population. The reliability of the tool will be tested through repeated measurements, and its validity will be assessed by comparing BPAT results with other validated asthma assessment tools. The data will be analyzed to evaluate the internal consistency, test-retest reliability, and construct validity of the BPAT in a clinical asthma population. The linguistic validation process will be conducted following the ISPOR Task Force guidelines, including forward translation, reconciliation, back-translation, and cognitive debriefing. The psychometric properties of the tool, including internal consistency, test-retest reliability, and construct validity, will be evaluated according to the COSMIN checklist standards. Additionally, participant eligibility will be defined as individuals who are diagnosed with asthma and can understand and respond to questions in Turkish. The study will also explore any cultural adaptations necessary for the Turkish version of the BPAT to ensure its cultural relevance and accuracy in assessments.

Background: Almost 3 billion people worldwide, including 89% people in Bangladesh, are exposed to harmful household air pollutants (HAP) emitted from combustion of biomass fuel (wood, agricultural residue, cow dung, etc.) used for cooking. While health risks associated with air-pollution have been reasonably well-studied in developed countries, there is little evidence on health benefits achievable by HAP reduction through clean fuel use such as Liquid Petroleum Gas, especially in low- and middle-income countries (LMICs). Rationale: In the earlier GEOHealth (Round-I) study, the investigators have shown that LPG for 24 months, reduced personal PM2.5 exposure by 58.2 percent which induced novel changes in innate immune and inflammatory responses in women but the changes in chronic cardio-pulmonary markers were not prominent, most likely due to short duration of follow up and probably impact of ambient pollution. Moreover, sustained use of LPG could be challenging as earlier GEOHealth (Round-I) study provided the cook stove and supply of LPG free of cost. A post-completion screening showed \>70% households continued using LPG albeit not exclusively. It is plausible that an intervention using mobile phone-based application can improve the exclusive use of LPG in the communities. Hypothesis: 1. The mobile phone based (mHealth) Behavioural Change Communication (BCC) intervention can be easily incorporated in Government policy that can promote adoption, and increase exclusive use of LPG in the communities. The long-term effect of HAP reduction can be associated with- 2. subclinical measures of cardio-vascular and pulmonary dysfunction. 3. balanced changes in innate/ inflammatory and adaptive immune function (vaccine response). Objectives: To evaluate 1. The effects of a scalable educational intervention (using mHealth application) on adoption and exclusive use of LPG. 2. The long-term effects of HAP reduction on subclinical measures of cardio-vascular and pulmonary dysfunction. 3. The long-term effects of HAP reduction on innate/ inflammatory immune function among women and children and to investigate the influence of HAP exposure on antibody response to vaccines (adaptive immunity). Methods: The investigators will conduct a large household level randomized controlled trial by educational intervention using mobile phone (mHealth) based technology. In addition, the investigators will continue following the cohort and will conduct rigorous and repeated personalized (24 hours) and area-wise (over 5 days) assessments of PM2.5 and black carbon (BC) exposure to examine the long-term effects of HAP reduction on subclinical measures of cardio-pulmonary and immune dysfunction including effect of HAP exposure on antibody response to vaccine. Outcome measures/variables: Personal and surrounding area PM2.5 and BC level will be measured at pre- and post-intervention. Lung function and lung pathology will be assessed through spirometry, Chest X-ray, and High-resolution Computed tomography of the chest (HRCT). Preclinical makers of cardiovascular diseases (CVD) will include blood pressure and EKG. Markers of metabolic dysfunction will be assesses by measuring HbA1c and fasting lipid profile. Immune function will be assessed by phenotyping of Immune cells, functional cytotoxic killer cells, oxidative stress of lymphocytes.

Briefly, during a one to two hour visit, subjects will provide written informed consent and then undergo: 1. brief medical history and vital signs, 2. full pulmonary function tests, 3. proton MRI, 4. spin-density, diffusion weighted, and/or dissolved phase 129-Xe MRI, 5. Low-dose thoracic CT Full pulmonary function tests including spirometry, plethysmography and diffusing capacity of carbon monoxide (DLCO), Multiple Breath Nitrogen Washout (MBNW) to measure Lung Clearance Index (LCI), and Forced Oscillation Technique (FOT) will be performed according to American Thoracic Society (ATS) guidelines. MedGraphics Elite Series, MedGraphics Corporation. St. Paul, Minnesota USA and/or nDD EasyOne Spirometer, nDD Medical Technologies Inc. Andover, Massachusetts USA will be used. All measurements will be performed in the Pulmonary Function Laboratory at Robarts Research Institute. Subjects will be placed in the 3T Magnetic Resonance (MR) scanner with one of three 129-Xe chest coils fitted over their torso and chest. Hearing protection will be provided to each subject to muffle the noise produced by the gradient radiofrequency (RF) coils. A pulse oximeter lead will be attached to all of the subjects to monitor their heart rate and oxygen saturation. MRI will be performed for up to a period of 30 minutes. All subjects will have supplemental oxygen available via nasal cannula at a flow-rate of 2 liters per minute as a precaution in the event of oxygen desaturation. Thoracic low dose CT will be performed with the same inhalation breath-hold volume and maneuver (nitrogen gas only) used for MRI to obtain participant-specific high resolution images of lung anatomy (tissue structure and airway morphology).

This study focuses on the markers that are derived from the interaction of 129Xe with pulmonary capillary red blood cells (RBCs). Specifically, the investigators focus on RBC transfer MRI, cardiogenic oscillations in 129Xe-RBC signal amplitude, and the 129Xe-RBC chemical shift. In addition to healthy volunteers, the population to be studied will consist of patients scheduled to undergo either transfusion or phlebotomy, those with dyspnea, those with a physician diagnosis of interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonias (NSIP), chronic hypersensitivity pneumonitis (cHP), and sarcoid, as well as those with either chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism.

The 3TR Consortium is the overall generator behind the 3TR-ABC study. The 3TR Consortium consists of 15 European countries and a total of 69 partners who collaborate on seven different autoimmune, inflammatory, and allergic diseases: chronic obstructive pulmonary disease, asthma, Crohn's disease, ulcerative colitis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis. The ambition of the consortium is to accelerate precision medicine by fundamentally increasing the knowledge of molecular pathways and mechanisms related to response and non-response to therapy. To date, the 3TR Consortium is the largest immunology project funded by the Innovative Medicine Initiative (IMI). The 3TR-ABC platform study is anchored in the so-called work package 8 (WP8) within the 3TR Consortium and will contribute with knowledge about the effect of biological therapies in severe asthma: With the advent of highly targeted biological therapies for severe asthma, several important questions arise; what determines a good clinical response versus non-response? Can we induce remission of severe asthma, and improve long-term outcomes? The 3TR-ABC study platform is a clinical trial platform and network, in which intervention-specific studies on different biologics are conducted. Via the 3TR-ABC study platform, conducting advanced translational studies in a real-life cohort of asthma patients is made possible, in collaboration with key opinion leaders and scientific experts in the field from across Europe. The 3TR-ABC study design includes a core study visit structure, which can be expanded or amended per study to suit individual focus points. Overall, the study design includes enrollment of bio-naïve patients with severe asthma, who have been assessed with systematic assessment, and who meet the criteria for commencing a biologic, according to national criteria in each country. Patients are then followed from the time of starting a biological treatment for three years, during which time they are followed at set time points as well as at the time of exacerbations, with sampling consisting of a core package and expanded packages, depending on the site. By using a range of state-of-the-art and novel methods for assessing immune activation, and applying advanced bioinformatics analysis methods, The investigators expect to be able to identify immune activation patterns and response profiles that will further our understanding of disease drivers in the treatment of refractory severe asthma. Furthermore, healthy participants and patients with mild/moderate controlled asthma will be acting as controls for baseline markers thus constituting a healthy as well as mild/moderate controlled asthma reference population. Benralizumab Cohort Study: The AIR-BIO-OCT study Allocation to biologicals occurs by means of asthma phenotyping including clinical parameters including OCS use and blood or sputum / bronchoalveolar lavage (BAL) eosinophils (reflecting Th2 high - Th2 low inflammation). It is unclear if and how biologics impact on airway remodeling and how they act within the airway wall and which airway cells are targeted in vivo, directly or indirectly by a reduction in eosinophils. Important pathophysiological features of asthma that relate to disease severity and prognosis are airway inflammation and remodeling, including an increase in airway smooth muscle (ASM) and extracellular matrix (ECM) alterations. Therefore, with the AIR-BIO-OCT substudy as part of the 3TR-ABC Study, next to performing a complete unbiased multi-omics approach the investigators also have some already identified multi-omics phenotypes within severe asthma that the investigators would like to investigate in a cohort of benralizumab users. As such extensive phenotyping before and after treatment, by combining exhaled breath VOCs (GC-MS and eNose) technology with minimal invasive omics (molecular) and innovative imaging technology by OCT, including polarization-sensitive OCT PS-OCT (impact of benralizumab on remodeling). Primary Objective Determine baseline biomarkers of remission after 1 year of biological therapy, defined as ACQ-5 \<1.5, post-bronchodilator FEV1 percent predicted ≥80% OR \>10% improvement as well as no exacerbations, or use of maintenance steroids for the past 12 months ("remission on treatment"). Secondary Objectives Determine baseline biomarkers of remission after 3 years of biological therapy. Additionally, i) Change in biomarker profiles in remission versus non-remission groups, ii) baseline and change in biomarker profile for a) each response outcome individually, b) Global evaluation treatment efficacy (GETE), patient and physician rated response, and c) 3TR agreed on a composite assessment of response, iii) determine the change in all response variables against baseline biomarker data and change in biomarkers as continuous variables. Exploratory Objectives: Novel analytical science approaches including but not limited to network and cluster analyses and partial least-squared discriminate analysis (PLSDA), topographical discriminant analysis of omic data derived from the biosamples collected at planned visits as well as daily FENO to determine possible novel biomarker signatures (including FENO) and relate to asthma remission, clinical response, interactomes of the multi-omic and clinical data, host-microbiome interactions. AIR-BIO-OCT substudy objectives Primary Objective: * To identify and measure an eNose/ volatile organic compound (VOC)- multi-omics extensive severe asthma phenotyping strategy before treatment with biologicals to reveal add-on response characteristics to better predict treatment response. * To identify and measure minimal invasive predicting "signature" of biological treatment response in severe eosinophilic asthma by extensive asthma pheno-endotyping using innovative minimal invasive exhaled breath technologies including eNose/VOCs and omics. Secondary Objective(s) * To measure airway remodeling (extracellular matrix and airway smooth muscle) after treatment with Benralizumab * Establish the reduction of extracellular matrix (ECM) and airway smooth muscle (ASM) by the standard - polarization-sensitive (PS) - OCT and endobronchial biopsy analyses after 6 months - 1 year of Benralizumab treatment. Study Design The 3TR-ABC study is a multicentre observational prospective cohort study that follows patients with severe asthma from the time of commencement of biological therapy and three years onwards. Healthy individuals and patients with mild/moderate controlled asthma are included as reference groups and will undergo the same baseline visit as patients with severe asthma. Informed Consent must be obtained from all participants who accept enrollment in the study in order to allow the collection of data and biological materials for the database and biobank, respectively. The study follows each patient with severe asthma at six visits over a period of three years. The first visit is the so-called baseline visit and is performed before the beginning of a biological treatment. This visit consists of a standard examination package, a site-specific extended package (i.e., tests in this package will only be done at specific sites), and an optional extended package (i.e., the participant decides). The remaining five visits are so-called follow-up visits and are made respectively 4 weeks, 16 weeks, 52 weeks, 2 years, and 3 years after the baseline visit. These visits consist of a follow-up sampling package and a site-specific extended package. An optional extended package is furthermore possible for the 4 weeks, 52 weeks, 2 years, and 3 years visits. Between scheduled visits, patients with severe asthma are asked to come for an extra visit if they experience a sudden exacerbation. Participants in the control groups will only be invited for the baseline visit. The AIR-BIO-OCT study is a sub-study within the 3TR-ABC Study performed in the Netherlands that will select severe eosinophilic asthma patients that start treatment with Benralizumab and will phenotype those patients (combining exhaled breath analysis and OCT technology) before and after 16 weeks and additional 52 weeks from the start of the biological. In the Netherlands, the AIR-Bio-OCT substudy consists of two parts: the first, aligned with the 3TR - ABC study, where samples of the abovementioned packages will be collected (n=34) and merged with the Benralizumab subjects recruited within the 3TR consortium (total 60-90 patients). The second part, additional bronchoscopy with standard and PS-OCT before and after 6 months-1 year will be performed (n=15).

The objective of this study is to test the hypothesis that over-the-counter amino acid supplement 5HTP (isolated from the plant Griffonia Simplifolia) reduces human allergic lung responses and consequently improves lung function. The primary outcome is the change in FEV1. We anticipate the 5HTP at the proposed doses will improve lung function as in preclinical studies that used clinically relevant 5HTP. Secondary outcomes will be blood eosinophil counts and reduced symptoms for anxiety/depression, as seen in changes in the anxiety-depression scores from questionnaires (CES-DC \& SCARED). The results from these studies have the transformative potential to influence approaches to improve lung function and asthma-associated anxiety/depression. * Aim 1: Test that 5HTP improves lung function in children with allergic asthma * Aim 2: Test that 5HTP reduces eosinophil numbers in the blood and nasal fluid of patients with asthma from Aim 1 * Aim 3: Test that 5HTP decreases lung inflammation, increases cortisol and prolactin without altering systemic plasma concentrations of 5HTP, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and dopamine

The three different doses of Atectura inhalation capsule via Breezhaler will be prescribed according to the approved label information in Korea, and the investigation for any additional diagnostic or monitoring will be not conducted for this study

The two different doses of Enerzair inhalation capsule via Breezhaler will be prescribed according to the approved label information in Korea, and the investigation for any additional diagnostic or monitoring will be not conducted for this study.

The primary efficacy objective is to assess the effect of BLU-5937 on 24-hour cough frequency in adults with refractory chronic cough (including unexplained chronic cough) at 24 weeks.

Allergic asthma being the most widespread and easily identifiable phenotype, accounting for 60-80% of cases.Previous studies have reported that nearly 90% of patients with severe asthma were cases of allergic asthma, in which Immunoglobulin E (IgE) plays a critical role.Omalizumab was approved as an anti-IgE humanized monoclonal antibody for the treatment of patients with poorly controlled moderate-to-severe asthma, and was the first targeted drug used in the field of asthma treatment.The drug was launched in mainland China in August 2017.whereas,the clinical application experience, effects, and relevant data in the domestic population still lacking.The aim of this study was to observe the efficacy and safety of omalizumab, and to investigate whether baseline clinical characteristics and biomarkers can predicted response and adherence to treatment.