San Sebastian, Guipuzcoa, Spain

A Study on COPD Phenotypes, Endotypes and Treatable Traits

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and multisystemic disease with progressive increasing morbidity and mortality. COPD is now widely accepted as a heterogeneous condition with multiple phenotypes and endotypes. The prevalence of COPD varied from 11.4 to 26.1% according to a multi-city study that surveyed the population with spirometry. The economic burden of COPD on society is enormous. In 2005, COPD ranked second as a respiratory cause for hospitalization and inpatient bed days in Hong Kong. In those >75 years of age, the hospitalization rate for COPD was as high as 2,225/100,000. The prevalence of moderate COPD, using the spirometric reference of FEV1/FVC ratio of <70%, among 1,008 elderly HK Chinese (age ≥60 years) in the community, were 19.6% and 11.9% in the male and female subjects respectively. The concept of "phenotype" is defined as the physical appearance or biochemical characteristic resulting from the interaction between the genotype and the environment. It is the observable characteristics of a disease, such as morphology, development, biochemical or physiological properties, or behaviour. Some phenotypes have a significant impact on prognosis, including symptoms, exacerbations, response to therapy, and rate of disease progression or mortality.1 On the other hand, an endotype is a subtype of disease defined functionally and pathologically by a distinct molecular/ pathophysiological mechanism or by distinct treatment responses. An example is type 2 high inflammation. The recognition of COPD phenotypes and endotypes has significantly impacted the management of the disease. Using biomarkers to identify specific COPD phenotypes has dramatically improved the success rate of novel drug development, increasing the probability of success in phase IIa trials from approximately 29% to 82%. This combined approach, incorporating COPD phenotypes and new biomarkers, is expected to revolutionize the management of COPD in the coming years. An example is a recent phase 3 clinical trial on Dupilumab in COPD patients. Dupilumab is a fully human monoclonal antibody which blocks the shared receptor component for interleukin-4 and interleukin-13. In COPD patients who had evidence of type 2 airway inflammation, as indicated by elevated blood eosinophil levels, those who received dupilumab experienced fewer disease exacerbations, improved lung function and quality of life, and less severe respiratory symptoms compared to those who received a placebo.8 Furthermore, treatable traits (TTs) are recognizable phenotypic or endotypic characteristics that can be assessed and successfully targeted by therapy to improve a clinical outcome in a patient with airway disease. The TTs must share 3 characteristics, including clinical relevance, being "detectable" (e.g., by phenotype or endotype), and being treatable (effective treatment is available and accessible and can improve patient clinical outcomes). A meta-analysis that assessed the TT approach to the management of obstructive airway diseases, which included studies of interventions targeting at least 1 TT from pulmonary, extrapulmonary, and behavioural/lifestyle domains, found that TT interventions were effective at improving health-related quality of life, hospitalizations, all-cause-1-year mortality, dyspnea score, anxiety, and depression. The healthcare system in Hong Kong is different from that of other places. Previous studies in Hong Kong only looked at specific endotypes; an example is the eosinophils cut-off to predict COPD exacerbations and the treatment effect of applying interventions to certain phenotypes, e.g. approaching the exacerbation phenotype with a comprehensive care programme. There is not much information on the overall phenotypes, endotypes, and TTs of COPD patients in Hong Kong. The characteristics of the patients would help to further assess whether the multi-TT approach can improve their outcomes. Primary outcomes: Characteristics of phenotype and endotypes and treatable traits and their changes over time Secondary outcomes: Characteristics of the relationships of phenotype and endotypes and treatable traits with exacerbations of COPD, mortality, lung function decline, symptoms and quality of life. Methods: This is a prospective observational study for a period of 3 years. Patients will be recruited from the out-patient general medical and respiratory clinics of the Prince of Wales Hospital. Also, patients admitted for acute exacerbation of COPD will be recruited upon discharge at the Prince of Wales Hospital. Inclusion criteria: 1. Patient with COPD with compatible history and lung function assessment according to Global Obstructive Lung Disease (GOLD): Patient has chronic respiratory symptoms (dyspnoea, cough, sputum production and exacerbations due to abnormalities of the airway (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow limitation. Lung function assessment with forced spirometry demonstrated the presence of a post-bronchodilator FEV1/FVC <70%. 2. Patient with age ≥40 years Exclusion criteria: 1. Serious disease that would hinder the patient from having follow-up for 3 years, e.g. late-stage malignancy, severe heart failure and severe renal failure not on dialysis. 2. Unable to provide written informed consent. Assessments: Patients will be recruited from the out-patient general medical and respiratory clinics of the Prince of Wales Hospital. Also, patients admitted for acute exacerbation of COPD will be recruited upon discharge at the Prince of Wales Hospital. i) Baseline The following parameters will be assessed at the baseline visit: - Demographics (age, gender, body height, body weight, occupation) - Characteristics (comorbidities) - COPD information (e.g. age of onset) - Spirometry - Exhaled nitric oxide level Forced Oscillatory assessment of airway resistance - 6 minute walk test - Exacerbations - Risk factors (e.g. smoking history, environmental and occupational exposure to pollutants) - Impact on daily activity and health related quality of life by MMRC, CAT and SGRQ - Treatment(s) during previous 12 months - Healthcare utilizations during previous 12 months Rehabilitation in the past 12 months - Nurse education programme in the past 12 months - Blood biomarkers (C-reactive protein, Immunoglobulin E and eosinophil levels) - Exhaled breath collection for assessment of volatile organic compounds ii) Telephone follow up every 6 months Exacerbations in the past 6 months (including exacerbations treated by systemic steroid, exacerbations treated by accident and emergency departments and treated by hospitalization) iii) Annual visits at year 1, year 2 and year 3 - Demographics (body height, body weight) - Spirometry - Exhaled nitric oxide level Forced Oscillatory assessment of airway resistance - Exhaled breath collection for assessment of volatile organic compounds - Exacerbations(including exacerbations treated by systemic steroid, exacerbations treated by accident and emergency departments and treated by hospitalization) - Impact on daily activity and health related quality of life by MMRC16, CAT17 and SGRQ - Treatment(s) during previous 12 months - Healthcare utilizations during previous 12 months - Blood Biomarkers (C-reactive protein, Immunoglobulin E and eosinophil levels) - New diagnosis - Mortality and its cause will be recorded should it occurred during the study period

Additive Effects of 4-7-8 Breathing Technique With Standard Management on Dyspnea, Pulmonary Function and Quality of Life in Patients With COPD.

COPD is a very common chronic respiratory disease with symptoms (dyspnea, cough, expectoration and/or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema)-- cause persistent, often progressive, airflow obstruction. Breathing exercises help to manage dyspnea associated with COPD. In order to manage respiratory conditions COPD patients are encouraged for nasal breathing techniques along with standard management. Hence the objective of the study is to compare the effects of 4-7-8 breathing along with standard management versus standard management alone on dyspnea, pulmonary function, and quality of life in patients with COPD.

Respiratory Syncytial Virus Infection in Exacerbations of Chronic Obstructive Pulmonary Diasease: the RECODE Study

A Clinical Study of TQC3721 Inhalation Powder in Patients With Chronic Obstructive Pulmonary Disease

Magnetic Stimulation of Diaphragm in Chronic Obstructive Pulmonary Disease

COPD is a life-threatening public health problem that starts with shortness of breath, continues with exacerbations, and the prognosis gradually worsens. In COPD patients, respiratory functions decrease due to changes in the airways in the advanced stages of the disease; dyspnea, cough, and sputum emerge as three important symptoms. Respiratory function limitations and symptoms caused by the disease also cause physical and psychological disorders such as peripheral muscle weakness, exercise intolerance, decreased quality of life, depression, and anxiety in patients. Diaphragm dysfunction also develops in COPD. In severe COPD, changes occur in the sarcomere length, enzyme activity, and mitochondrial density of diaphragm muscle fibers. Recurrent COPD attacks also negatively affect diaphragm dysfunction. Due to diaphragm dysfunction, patients' exercise tolerance and daily living activities decrease even more after attacks; their quality of life decreases. The aim of treatment and care in COPD is to prevent progression, reduce symptoms, prevent and/or treat recurrent acute attacks, protect respiratory functions in the long term and prevent functional decline, increase exercise capacity, reduce complications and protect and increase quality of life. Since drug therapy alone is insufficient to achieve these goals, rehabilitation practices should also be a part of the treatment in addition to drug therapy. Oxygen therapy, nutritional support, pulmonary rehabilitation (PR) approaches are also among the supportive and palliative treatment methods. In the last twenty years, the negative effects of systemic symptoms on the functions of patients in COPD patients have accelerated the development and use of PR. The main goals of PR are to reduce symptoms, bring the person's functional and emotional status to the best possible level, increase participation in daily life and quality of life, and reduce health-related expenses by reversing or stabilizing the systemic effects of the disease. PR has been shown to be the most effective non-pharmacological intervention to improve health status in COPD patients. The main component of PR programs is exercise; which includes aerobic exercise, strengthening exercises, inspiratory muscle training, controlled breathing techniques, bronchial hygiene techniques, stretching exercises, relaxation exercises, as well as water exercises, pilates and yoga programs. There are also daily life activity practices and assistive device training exercises. Considering the weakness of peripheral muscle and diaphragm muscle strength in COPD patients, alternative strengthening methods for these muscles are important. rPMS is a physical therapy method based on the interaction between a high-intensity electromagnetic field and the human body. The electromagnetic field is generated by a coil placed in the applicator. Depending on the frequency of stimulation and the intensity of the electromagnetic field, it has analgesic, muscle relaxant or muscle strengthening effects. The rPMS method, which is one of the alternative treatment methods that strengthens the diaphragm, does not require direct contact with the skin. Since it can be applied over clothes, the patient does not need to undress or prepare the skin. It is not painful like other invasive methods, so the patient's compliance will be higher and the possibility of abandoning the treatment is less. The rPMS application is fast and easy to use, because there is no need to connect a stimulating electrode to the patient. In this study, it is planned to investigate the hypothesis that adding rPMS of the diaphragm to the PR program in individuals with COPD would lead to more improvement in exercise capacity, diaphragm muscle thickness, and consequently, symptoms. In line with this hypothesis, the aim of the study was to evaluate the effectiveness of repetitive peripheral magnetic stimulation (rPMS) to increase diaphragm strength in addition to the PR program applied in COPD, and to investigate the effect of this method on exercise capacity, diaphragm muscle thickness and symptoms. This is a prospective, randomized, sham-controlled, single-blind, experimental study. Patients who admitt to Ankara University Medical Faculty Hospital Physical Medicine and Rehabilitation Clinic for PR and have stable COPD diagnosis will be invited to the study. This study will be conducted within the scope of good clinical practices and written informed consent forms will be obtained from all patients. The sociodemographic information, smoking history, duration of COPD, presence of co-morbidities, regularly used medications, and other medical history of the patients will be recorded. Patients will be randomized into two groups. Both groups will receive 24 sessions of standard PR programs. Intervention group will also receive repetitive peripheral magnetic stimulation (rPMS) to strengthen the diaphragm muscle. Patients will be evaluated at baseline and at the end of the program. The assessments will include cardiopulmonary exercise test (CPET) for dynamic respiratory functions and VO2max and six-minute walk test to determine functional exercise capacity, Saint George Respiratory Questionnaire (SGRQ) for health specific quality of life, Transitional Dyspnea Index (TDI) measuring changes in shortness of breath, Modified Medical Research Council (mMRC) Dyspnea Scale and diaphragm muscle thickness measurement with ultrasonography.

InvEstigating oeStrogen Signalling and the Effect upoN the exTracelluar Matrix In pAtients With Obstructive Lung Disease

The investigators are investigating the effect of oestrogen and oestrogen loss on the lungs. This is important to because lung diseases are a growing problem globally. In people suffering from Asthma and chronic obstructive pulmonary disease (COPD), women are more likely to die from lung disease than men. The researchers believe this global difference is due to sex hormones. Women have more oestrogen than men. Other studies have shown that oestrogen affects the lungs through the immune system. The researchers want to know the effect that oestrogen has on the lungs in people suffering from Asthma and COPD by comparing this to people with no lung disease. The researchers are also particularly interested in what happens at the point where women lose oestrogen naturally, which is the menopause. They want to understand the effect of oestrogen in younger women and compare this to women who have experienced the menopause. This is an observational study. Therefore, the participants will have a baseline visit and another subsequent visit (or multiple visits which are optional) and the researchers will compare the changes in their oestrogen levels, lung function and immune system response. To understand the differences mentioned above in the body we require samples and questionnaires to be filled out at face-to-face visits. All participants will be given the opportunity to opt into different streams of visits which vary between 12 months and 24 months.

A Study to Evaluate the Safety and Efficacy of HL231 Solution for Inhalation in Patients with COPD

Make Every Step Count: Personalised Music Feedback to Walking for People Living With COPD

Previous research has shown that adherence to the prescribed walking exercise intensity is challenging for individuals with COPD and that methods to provide further support are needed. Using activity monitors and trackers to give feedback can increase the walking exercise participation of people living with COPD. However, it has been reported that more than half of steps taken during exercise were below the prescribed pace. It is possible to individually prescribe exercise intensity by deriving cadence (steps taken per minute) from the ISWT and ESWT using activity monitor. Furthermore, activity monitors have been used to measure level of adherence to the intensity of the prescribed walking exercise prescriptions in the context of PR and chronic respiratory diseases. Listening to music in daily life can decrease stress and improve the psychological well-being. Implementing music to enhance exercise performance has been utilised with different populations. Auditory feedback in the form of listening to music is one example where exercising to music can be utilised as distraction from fatigue perception or used as a motivational tool to exercise in a healthy population. Previous studies have investigated the effect of listening to music while exercising at different intensities and music tempos on fatigue perception and have shown a positive effect in decreasing the perception of fatigue. In addition, the effect of choosing the preferred versus non-preferred music genre on repeated sprints showed significant improvement in motivation to exercise and lower perceived exertion rates in the preferred music genre group. Similarly, in COPD, listening to music as distractive auditory stimuli while exercising decreases breathlessness and fatigue symptoms resulting in increased aerobic capacity and HRQOL. In another study, individuals with COPD who listened to music while performing high-intensity exercise, showed a reduction in dyspnoea, which was associated with higher tolerance of high-intensity exercise as measured by endurance time. The findings of a previous study showed that participants who listened to music can perform significantly more exercise compared to participants who listened to grey noise or silence. Paced walking to music with COPD participants showed significant improvement in dyspnoea, exercise tolerance, HRQoL and fatigue. In the context of unsupervised walking exercise among individuals living with COPD, paced walking to interval beeps sound as such in metronomes to maintain the walking exercise intensity had been investigated previously. In a prospective observational clinical trial, the effect of home-based PR on exercise capacity and HRQoL using paced walking to metronome was investigated. The results showed improvements in maximal exercise capacity (six minute walk test: 6MWT) and HRQoL (SGRQ). However, the constant rhythm such as in metronome style feedback may not be interesting overtime which can make walking exercises less engaging and lead to reduced motivation for long-term adherence. Combining the effect of paced walking when listening to 'metronome style' feedback and preferred music to support walking exercise might offer a more enjoyable way to coach people living with COPD to walk for exercise at their prescribed intensity. This principle has been investigated in adult without reported diseases population using a mobile application (app), the BeatClearWalker (BCW), as shown in the link (https://youtu.be/MLy4GA8_eUc?si=oQL3mklA2bRKbnQl). The BCW is a fitness smartphone application that monitors walking cadence and helps individuals to walk at their individually-prescribed cadence and maintain that cadence. The app is designed to work on smartphones run by Android software only. Despite a considerable number of fitness applications that monitor walking distance, this is the first application designed to support walking and provide real-time feedback about cadence through music sound quality. The application allows service users to listen to any music while walking and apply dynamic live audio feedback to help individuals to walk at and maintain the pre-set individualised target walking cadence which can be entered on the application. The real-time, hands-free audio feedback is noticeable and designed to disrupt the quality of the played music. The feedback comes in two forms: (1) clear music, similar when listening to any typical music played in streaming music player or (2) degradation of music audio quality. The music will play without effect if the individuals walk at or above their targeted cadence. Once the walking cadence drops below the targeted, the quality of the music will be degraded and will return to normal once the individual reaches the targeted cadence again.

Evaluation of Nasal Biomarkers for Objective Assessment of Disease Severity in Respiratory Disorders

Chronic Airway Disease and Multimorbidity Cohort

The Chronic Airway Disease and Multimorbidity (CAM) Cohort is a nationwide, prospective, multicenter, longitudinal observational study aimed at understanding the epidemiology and impact of multimorbidity on patients hospitalized due to exacerbation of chronic airway diseases (CAD), including chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis. The study will enroll 2,000 patients across 9 medical centers in China, following their health trajectory for one year post-hospitalization. Objective The primary objective is to assess how multimorbidity influences treatment outcomes, hospitalization length, and readmission rates in CAD patients. Secondary goals include analyzing comorbidity patterns, their effects on symptom burden, quality of life, pulmonary function, healthcare costs, and utilization. Study Design Participants meeting inclusion criteria will be recruited through hospital advertisements and professional referrals. Upon providing informed consent, demographic, clinical, and laboratory data will be recorded during baseline hospitalization. The study employs standardized questionnaires and clinical tools such as mMRC, CAT, and SGRQ for quality-of-life assessments. Specimens, including blood, bronchoalveolar lavage fluid (BALF), and sputum, will be collected and stored for biomarker analysis. Imaging studies such as chest CT and echocardiography will evaluate disease severity and cardiac function. Patients will be systematically followed at 1, 3, 6, 9, and 12 months post-discharge to record disease progression, treatment adherence, exacerbations, and outcomes. Data Collection Demographics and Risk Factors: Age, gender, smoking history, family history, and occupational exposures. Symptoms: Disease-specific tools such as CAT/mMRC(COPD), ACQ-7 (asthma) and BEST (bronchiectasis) will quantify symptom severity. Quality of Life (QoL): SGRQ for COPD, QoL-Bronchiectasis for bronchiectasis, and mini-AQLQ for asthma patients. Laboratory Data: Arterial blood gas, blood count, liver and renal function, inflammatory markers, and allergy panels. Muti-morbidities: Systematic documentation of pulmonary and extrapulmonary comorbidities, including their diagnosis, treatment, and severity. Outcome Measures: The primary outcomes are hospital length of stay and re-exacerbation rates. Secondary outcomes include changes in pulmonary function, QoL, mental health indices, imaging findings, and healthcare resource utilization. Quality Control Data will be managed using an electronic data capture(EDC) system, with built-in validation to ensure accuracy. Periodic data audits and centralized training for research coordinators will enhance data integrity. Monitoring committees will address data discrepancies promptly. Ethics and Dissemination The protocol complies with the Declaration of Helsinki and has received approval from ethics committees of all participating centers. The findings will inform clinical guidelines, emphasizing the integration of multi-morbidity management in CAD care. This study bridges significant knowledge gaps in CAD management, particularly concerning multimorbidity in hospitalized patients, aiming to enhance evidence-based clinical practices.