Therapeutic Advances in Respiratory Disease最新文献

Background: The role of the gut-lung axis in respiratory disease is increasingly recognised. Much emphasis has been placed on gastro-oesophageal reflux disease; however, oesophageal dysmotility may also play a significant role. Azithromycin, a known prokinetic, has been shown to be of major benefit in a number of respiratory diseases, but the relationship between oesophageal function and the lung has not been examined.

Objectives: We assessed the feasibility of performing continuous cough monitoring and repeated high-resolution oesophageal manometry (HROM) in patients with chronic respiratory disease.

Design: We conducted an open-label, single-arm, feasibility trial.

Methods: Azithromycin 250 mg once daily was given to patients with chronic respiratory disease who reported a chronic cough. All participants were monitored continually for at least 1 week prior to and 4 weeks after azithromycin with the Hyfe Cough Tracker. Participants also had HROM performed at two time-points, immediately before and 4 weeks after initiation of azithromycin. Feasibility outcomes pertaining to recruitment, data quality, and acceptability of trial processes were assessed. Exploratory outcome data for metrics of oesophageal function were also analysed.

Results: A total of 30 participants (57% female, mean age 65.2 (SD = 11.3)) were recruited over a 10-month period, giving a recruitment rate of three patients per month in a single centre. A total of 87% (n = 26) of participants completed all three study visits. All pre-specified data quality outcomes met their 'green' traffic light stop-go criteria. HROM demonstrated that the majority (52%) of participants had abnormal oesophageal function, as defined by the Chicago Classification, at baseline. Changes in oesophageal function were not significantly associated with changes in objective or subjective cough measures, except for a weakly negative correlation with the Hull Airway Reflux Questionnaire score.

Conclusion: A large-scale trial examining the effect of azithromycin on the relationship between oesophageal function and cough in respiratory disease is feasible and acceptable to patients.

Trial registration: This trial was prospectively registered ClinicalTrials.gov ID: NCT05469555.

Background: Joubert syndrome (JS) is an autosomal recessive disorder with a distinctive mid-hindbrain malformation known as the "molar tooth sign" which involves the breathing control center and its connections with other structures. Literature has reported significant respiratory abnormalities which included hyperpnea interspersed with apneic episodes during wakefulness. Larger-scale studies looking at polysomnographic findings or subjective reports of sleep problems in this population have not yet been published.

Objectives: The primary objectives were (1) compare a large group of children with JS and their unaffected siblings for caregiver-reported sleep difficulties. Secondary objectives were (1) present new polysomnography (PSG) data on our JS cohort; (2) review sleep disordered breathing (SDB) in other rare congenital hindbrain anatomic abnormalities.

Design: We conducted a cross-sectional study on a cohort of 109 families affected by JS.

Methods: Pediatric Sleep Questionnaire (PSQ) and the Children's Sleep Habits Questionnaire (CSHQ) along with general medical health information focused on respiratory and sleep problems were mailed to all patients and families. Caregivers were asked to complete the survey for both children with JS and unaffected siblings, if any. Baseline diagnostic PSG was retrospectively reviewed for those with available studies, and the sleep parameters were compared to a referent cohort.

Results: Study participants with JS were older than their unaffected siblings (p = 0.02). Genetic mutations were available for 41 out of 118 individuals, with the most common mutation being MKS3 (31.4%). Patients with JS had higher scores in the PSQ compared to their unaffected siblings (p < 0.001). PSG data showed severe SDB with apnea-hypopnea index (AHI) of 23 ± 15 events/h in patients with JS. Events were primarily obstructive (obstructive AHI 18 ± 15 events/h vs central AHI 4 ± 4 events/h). Abnormal sleep architecture with increased arousal indices, decreased efficiency, and more time awake and in light sleep or wakefulness when compared to the referent data.

Conclusion: SDB is common and severe in patients with JS, and the significantly greater obstructive component reported in this cohort makes it necessary to perform complete PSG studies to address or prevent clinical manifestations in this at-risk population. PSQ could represent a viable method to screen for SDB in JS.

Over the past decade, major clinical advances have been made in the healthcare and therapeutic development for cystic fibrosis (CF), a lethal genetic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. CFTR modulators represent innovative treatments that directly target the primary defects in the mutated CFTR protein and have demonstrated significant clinical benefits for many people with CF (pwCF) who are eligible for these treatments. In particular, the triple combination therapy composed of elexacaftor, tezacaftor, and ivacaftor (ETI) has changed the CF therapeutic landscape by significantly improving lung function, quality of life, and predicted survival rates. Here, we provided a comprehensive summary of the impact of ETI on clinical outcomes and the need for further research on long-term efficacy, side effects, pregnancy, possible drug-drug interactions, and extra-pulmonary manifestations. Moreover, a significant number of pwCF are unresponsive to these drugs or cannot afford their high costs. We, therefore, discussed health inequity issues and alternative therapeutic strategies under development aiming to obtain effective therapies for all pwCF.

Background: During the COVID-19 pandemic, telemedicine became crucial for monitoring chronic conditions, including respiratory diseases.

Objectives: This study, part of a larger cohort of COVID-positive patients, focuses on individuals with chronic obstructive pulmonary disease (COPD) monitored through an active home surveillance system (COD19).

Design: Longitudinal telematic active surveillance study.

Methods: The study included COVID-19-positive patients in home isolation, quarantined workers, and those discharged from ASST hospitals or emergency departments. At discharge, patients received a letter with isolation guidelines, a COD19 kit (oxygen meter, thermometer, protective devices), and instructions for monitoring clinical parameters. Regular phone check-ins by physicians were conducted, starting within 12 h of activation. A secure platform COD19 enabled data collection and communication between patients, healthcare providers, and regional authorities.

Results: The study involved 1288 patients, including 226 (17.5%) with COPD, who were older (p < 0.001), had a higher BMI (p = 0.006), and were more frequently admitted from home isolation (p < 0.001). COPD patients also had higher mean body temperature (p = 0.011) and respiratory rate (p = 0.035), with a non-significant trend toward lower SpO₂ values. Monitoring outcomes indicated that COPD patients were more likely to require higher levels of care (p < 0.001), and the only two deceased patients were from this group. The remote monitoring service received positive feedback, with a median answering ratio of 92%, reflecting strong patient participation and manageable monitoring processes.

Conclusion: The findings underscore telemedicine's effectiveness in COPD management, ensuring continuity of care and smooth home-to-hospital transitions. The system enhanced accessibility, enabling consistent monitoring and timely interventions. As healthcare evolves, telemedicine remains a key tool in improving patient care and accessibility.

Background: Asthma is one of childhood's most prevalent chronic conditions significantly impacting the quality of life. Current asthma management lacks real-time, objective, and longitudinal monitoring reflected by a high prevalence of uncontrolled asthma. Long-term home monitoring promises to establish new clinical endpoints for timely anticipation. In addition, integrating eHealth interventions holds promise for timely and appropriate medical anticipation for controlling symptoms and preventing asthma exacerbations.

Objectives: This study aims to provide a pragmatic study design for gaining insight into longitudinal monitoring, assessing, and comparing eHealth interventions' short- and long-term effects on improving pediatric asthma care.

Design: The CIRCUS study design is a cohort multiple randomized controlled trial (cmRCT) with a dynamic cohort of 300 pediatric asthma patients.

Methods: The study gathers observational and patient-reported measurements at set moments including patient characteristics, healthcare utilization, and asthma, clinical, and environmental outcomes. Participants are randomly appointed to the intervention or control group. The effects of the eHealth interventions are assessed and compared to the control group, deploying the CIRCUS outcomes. The participants continue in the CIRCUS cohort after completing the intervention and its follow-up.

Results: This study was ethically approved by the Medical Research Ethics Committee (NL85668.100.23) on February 15th, 2024.

Discussion: The CIRCUS study can provide a rich and unique dataset that can improve insight into risk factors of asthma exacerbations and yield new clinical endpoints. Furthermore, the effects of eHealth interventions can be assessed and compared with each other both short- and long-term. In addition, patient groups within the patient population can be discerned to tailor eHealth interventions to personalized needs on improving asthma management.

Conclusion: In conclusion, CIRCUS can provide valuable clinical data to discern risk factors for asthma exacerbations, identify and compare effective scalable eHealth solutions, and improve pediatric asthma care.Trial registration: The protocol is registered at ClinicalTrials.gov (NCT06278662).

SummaryWhat is this summary about?• The Asthma Impairment and Risk Questionnaire (AIRQ^®) has been designed and tested to measure patients' levels of asthma control in a healthcare setting.• Unlike other available questionnaires that only assess asthma symptoms that can be bothersome or limit a person's activities and quality of life (impairment-related symptoms), the AIRQ also includes questions related to risk of an asthma attack. This allows for a broader measurement of asthma control and a prediction of the chance of having future asthma attacks.• AIRQ scores are linked to a patient's own experience of their health and how it impacts their daily life (health-related quality of life).• The AIRQ may make it easier for patients and healthcare professionals to have shared decision-making discussions that can lead to better asthma care and asthma outcomes.• This document summarizes several published studies of the AIRQ in people with asthma.

Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a progressive and high-risk subtype of PAH, with outcomes generally worse than those seen in idiopathic PAH. Early recognition and treatment are essential for improving survival, yet early-stage CTD-PAH remains challenging to identify, particularly for non-specialist clinicians. The 2022 ESC/ERS guidelines introduced several key updates that support an earlier diagnosis and more targeted management. These include a revised echocardiographic threshold for pulmonary hypertension probability (tricuspid regurgitation velocity >2.8 m/s), a lowered hemodynamic definition of PAH (mean pulmonary artery pressure >20 mmHg and pulmonary vascular resistance >2 WU), and a preference for annual screening using the DETECT algorithm in asymptomatic systemic sclerosis (SSc) patients. Additionally, novel therapeutic targets such as the activin/TGF-β pathway have been incorporated into updated treatment algorithms. Although CTD-PAH remains associated with worse outcomes than idiopathic PAH, recent advances in screening, risk assessment, and targeted therapies have begun to improve the trajectory of the disease. Early detection, personalized treatment, and comprehensive care are now key to transforming this high-risk condition into a more manageable one.

Background: Nontuberculous mycobacterial lung disease (NTM-LD) is a chronic infection of the lungs with a high symptom burden. NTM-LD treatment is typically long and complicated, which can impact quality of life and mental health. Increased support for psychological challenges is a priority for this population.

Objectives: We describe integrating psychological care into a multidisciplinary outpatient NTM program, patient characteristics, and results of patient-reported outcomes (PRO) screening (of depression, anxiety, fatigue, health-related quality of life, quality of life, and Top Problems).

Design: Retrospective observational cohort study design.

Methods: Processes and structure around psychology integration are described. Descriptive data obtained via retrospective chart review (IRB approved) are presented on patient sociodemographic factors, psychiatric medication and psychotherapy use, and results of PRO screenings with NTM-LD patients anticipated to start NTM antibiotic treatment or already on treatment. Relationships between variables were examined using nonparametric statistics.

Results: From 2020 to 2024, 175 patients with NTM-LD were screened. Patients were on average 65.7 ± 9.8 years old, female (74.2%), white (91.4%), and on Medicare (69.1%). On average, this group experienced a moderate degree of socioeconomic disadvantage; 94.9% of patients lived in areas with a mental health provider shortage, and 42.3% lived in medically underserved areas. Patients reported considerable rates of mild or higher depression (54.3%) and anxiety (32.0%). Many utilized psychiatric (52.6%) or pain (20.6%) medications, while engagement in psychotherapy was low (5.1%). Patients reported impacts on quality of life, fatigue, and health-related quality of life, and the most common Top Problems were: "Shortness of breath, Breathlessness, Getting winded," "Fatigue/Low energy," and "Cough/Choking."

Conclusion: A licensed psychologist was successfully integrated into the NTM program. The disparity between PRO results and psychotherapy engagement highlights a key opportunity for mental health interventions. Integrated psychological services may provide streamlined access to mental healthcare.