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).

Acute asthma (or asthma exacerbation) is common and costly. In the USA, acute asthma accounts for approximately 2 million emergency department (ED) visits per year; approximately 10-20% of patients are admitted and, among those discharged, approximately 15-20% relapse (i.e., return to the ED for further treatment of their index exacerbation). A 2000 Cochrane review evaluated if starting inhaled corticosteroids (ICS) at ED discharge would lower risk of relapse during the 2-3 weeks after the ED visit. The meta-analysis included three randomized controlled trials (RCTs) and found borderline significant evidence that ICS initiation lowered risk of relapse during the 2-3 weeks after ED discharge (total n=909 patients; OR 0.68; 95%CI 0.46-1.02). For decades, asthma experts have tried to increase ED-based prescribing of ICS to ED patients with asthma but uptake has been slow. In addition to reluctance among ED clinicians to prescribe a "lifelong" medication, a challenge has been patients' perception that they do not receive any immediate symptom relief from the new (ICS only) inhaler - i.e., "it does not work as well" as their regular (albuterol) inhaler. FDA approval of Airsupra (with both albuterol and budesonide in one inhaler) provides a unique opportunity to introduce ICS (along with albuterol) to ED patients with acute asthma. The proposed trial is a cluster randomized, open-label, intervention vs usual care, controlled study on the effect of ED initiation of Airsupra on acute asthma recurrence at 3 months (primary outcome) - i.e., a combination of acute asthma "relapse" (by 3 weeks) plus subsequent exacerbations. The trial is powered to assess a 33% reduction in recurrence at 3 months and will have ample power to explore asthma control, both overall and in important subgroups (e.g., stratified by age, sex, race/ethnicity, BMI, current asthma medications, and number of ED visits for acute asthma in the past year). Randomization of sites will be stratified by US region to increase likelihood that the two groups are similar at baseline. Patients will be enrolled by members of the Multicenter Asthma Research Collaboration (MARC), within the Emergency Medicine Network (EMNet). This research network was founded in 1996 with the original goal of performing clinical research on acute asthma. Massachusetts General Hospital is the EMNet Coordinating Center and will not participate in patient enrollment. Patient inclusion criteria include: acute asthma (i.e., fulfill American Thoracic Society criteria for asthma; age 18-54 years (to minimize contamination by COPD and to permit testing of effect modification by age); decision by ED attending to discharge patient to home on short course of systemic corticosteroids (to "validate" that patient truly had an asthma exacerbation); and informed consent. Patient exclusion criteria include: prior diagnosis of COPD, use of systemic corticosteroids in the past 2 weeks (to avoid enrollment of severe persistent asthma or patients presenting to ED with an acute asthma relapse, rather than their index presentation of acute asthma); comorbid complications (e.g., concurrent pneumonia); lack of a working cell phone and working email address (having both is common today and will increase follow-up rates); expected lack of availability for text and/or telephone follow-up at approximately 3, 6, and 12 weeks after the ED visit; or prior enrollment in this study. All patients will undergo a short, structured interview in the ED and a focused ED chart review, using previously developed instruments for ED-based asthma research. Site investigators will enter these data into a REDCap database created and managed at the EMNet Coordinating Center in Boston. Based on their random site assignment (intervention vs usual care), intervention sites will put enrolled patients on a short course of systemic corticosteroids (e.g., prednisone 50 mg daily x 5 days) and Airsupra PRN (rescue inhaler). Usual care sites will manage patients per usual care. All patients will receive a brief educational handout about asthma. At approximately 3, 6, and 12 weeks after the ED discharge, EMNet staff will follow-up with patients about their clinical course (including acute asthma relapse, asthma control, medication use), and potential adverse effects from any of the medications prescribed at ED discharge. Most follow-up assessments will be by telephone interview, but texts will be used per patient preference and/or to increase completeness of follow-up. Asthma control will be assessed using the AirQ, a 10-item instrument. EMNet staff will enter data into the REDCap database. Patients will sign medical release forms so that EMNet staff in Boston can collect medical records for the 12 months before enrollment and the first 3 months after enrollment. These records will come from the enrolling hospital or hospital system/network, along with the patient's primary care provider and, when applicable, their asthma specialist (allergist/immunologist, pulmonologist, asthma center). EMNet staff will review these medical records to identify repeat asthma exacerbations (ie, recurrence) and the patient's current medications at the end of the 3-month follow-up period. EMNet staff will enter data into the REDCap database. The primary outcome is acute asthma "recurrence" (i.e., any urgent or unscheduled visit to a clinician for worsening asthma symptoms) during the 3 months after the ED visit. This outcome differs from acute asthma "relapse" which is typically assessed during the 3 weeks after the ED visit; prior research indicates that symptoms of an exacerbation typically resolve by 1-2 weeks while biochemical evidence of the exacerbation resolves by 3 weeks. The frequency of recurrence in this unique, ED-based population is not known - but the investigators' best estimate for the usual care group is approximately 33% (i.e., they will experience 15% relapse in the first 3 weeks then additional events during the 9 weeks of fall/winter that follow.) The main secondary outcome will be asthma control at 3 months after the ED visit. Other secondary outcomes include acute asthma relapse (3 weeks) and post-ED initiation of Airsupra (any time during follow-up). Data analysis will describe patient characteristics, overall and in the two randomly allocated groups (15 intervention sites, 15 usual care sites). The primary outcome (acute asthma recurrence at 3 months after the index ED visit) will be analyzed using time-to-event data, in both unadjusted and multivariable models. Covariates will be major sociodemographic factors (e.g., age, sex, race/ethnicity, insurance) and clinical factors with an observed association (P\<0.20) with the recurrence outcome. The main secondary outcome (3-month asthma control) will be compared using t-test or Mann-Whitney U-test, as appropriate. Repeated measures are not necessary since the investigators will focus on 3-month asthma control; asthma control at baseline is non-interpretable in the context of the index exacerbation. The investigators will not do an interim analysis given the relatively short study enrollment, across 30 centers, and given the demonstrated safety of Airsupra (per FDA approval). Power calculations, based on acute asthma recurrence at 3 months (with an estimated intra-cluster correlation \[ICC\] of 0.02), suggest that 1290 patients are needed to detect a 33% reduction in recurrence (e.g., 22% recurrence in the Airsupra group vs. 33% recurrence in the usual care group). The main secondary outcome, asthma control, will require fewer patients. The investigators anticipate 70% follow-up of enrolled patients at 3 months and, therefore, have increased the target sample size to 1860 total patients (930 per arm; 62 per site). Based on experience with ED-based asthma research since the 1990s, the investigators believe that each site, over 4-5 months (August to December), can enroll at least 62 adult patients with acute asthma. (30 sites x 62 patients/site = 1860)

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 GENESIS study is a multicenter, prospective, non-interventional, clinical study with a target of 12,000 subjects and an anticipated total duration of 36 months. The aim of study GENESIS is to provide a pilot map of HLA genetic variation in the Greek population in order to be used in medical research and for possible clinical applications (evaluation of possible correlations with selected underlying diseases). During the study, each subject will conduct one visit to the participating cite, in which they will provide: 1. Demographic information \[i.e. date of birth, gender, race, ancestry (including information about the subject's grandparents' birthplace), height, weight\], 2. Other information about smoking/vaping, alcohol consumption, arterial blood pressure, diagnosed diseases (if any), current treatments (if any), and 3. Recent (up to 12 months prior to sample collection) results if/when are available from clinical lab tests such as blood count (Hct, Hb, RBC, WBC, PLT count), including a metabolic panel, liver enzymes and biochemical parameters (Glu, HbA1c, TC, TG, LDL-C, HDL-C, ALT, AST, ALP, γGT, bilirubin, LDH, insulin, C-peptide). Upon completion of the data registry, two buccal swabs will be collected per subject and they will be stored at ALTP premises until their shipment to Galatea.Bio. All buccal swab samples will be subjected to genetic material (DNA) extraction. The DNA samples will be further proceeded for HLA genotyping analysis. A follow up analysis will be performed in selected DNA samples via full low-pass whole genome sequencing (LP-WGS), which aims to further investigate the association between the HLA region and autoimmune diseases. Upon completion of the analysis, an individualized ancestry report will be securely made available to all study subjects which they can access, as and if they elect to.