Therapeutic Advances in Respiratory Disease最新文献

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).

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.

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.

Background: Chronic cough (CC) has a negative effect on patients' quality of life and everyday activities. Emotional reactions are an important aspect of how patients deal with illness, and CC can lead to feelings of uncertainty, loss of control, helplessness, self-consciousness, embarrassment, worry, fear, frustration, irritability, and anger.

Objectives: To assess the emotions related to bouts of cough in patients with refractory or unexplained chronic cough (RCC/UCC), using a validated questionnaire.

Design: This was a multicenter, non-interventional study.

Methods: Patients with RCC/UCC were recruited from hospital outpatient clinics in Spain. The impact of RCC/UCC on patients' emotions was assessed using the self-reported Discrete Emotions Questionnaire (DEQ), which assesses eight distinct situationally induced state emotions, scored on a Likert scale from 1 to 7, with higher scores indicating that the emotion is experienced to a greater degree.

Results: The survey was completed by 190 patients (148 women, 42 men; mean age 58.0 years) of whom 120 had RCC and 70 had UCC (mean cough duration 6.3 years). Highest mean (SD) scores were seen for the anger subscale (3.6 (1.7)) and anxiety subscale (3.3 (1.6), followed by the disgust (2.6 (1.5)), fear (2.6 (1.7)), and sadness (2.5 (1.5)) subscales. The same pattern was seen in subgroups by gender and by diagnosis (RCC or UCC). There were no significant differences in mean scores for any subscale between patients with RCC and those with UCC. Cough severity and the presence of cough-related stress urinary incontinence (SUI) were independently associated with negative emotion subscale scores.

Conclusion: Among patients with RCC/UCC, bouts of cough triggered negative emotions such as anger, anxiety, disgust, fear, and sadness, as evaluated using a validated questionnaire. Results were similar for RCC and UCC. Increasing cough severity and the presence of SUI were independently associated with higher (worse) scores for negative emotions.

Background: Afatinib is indicated for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, including uncommon mutations. However, the differences in survival benefits between patients with different types of EGFR mutations remain unclear.

Objectives: This study aimed to compare the effectiveness of afatinib treatment in patients harboring the EGFR-G719X mutation with that in patients carrying other uncommon EGFR mutations.

Design: This was a retrospective study.

Methods: Ninety-two patients with locally advanced and metastatic NSCLC, of whom 49 patients with EGFR-G719X mutations that were both single and compound, and 43 patients harbored other uncommon EGFR mutations, who were treated with afatinib as first-line treatment. The patients were followed up and evaluated every 3 months or when there were symptoms of progressive disease. The endpoints were the objective response rate (ORR), time-to-treatment failure (TTF), and overall survival (OS).

Results: The average ages of patients with the EGFR-G719X and uncommon EGFR mutations were 62.7 years and 63.1 years, respectively. There were no significant differences in sex or smoking history between the two groups. In total, 28.6% of patients with the G719X mutation and 23.3% of patients with other mutations had brain metastases. The ORR of patients with the G719X mutation was 79.6%, which was 10% higher than that of patients with other EGFR mutations. Patients harboring the EGFR-G719X mutation had median TTF and median OS periods of 19.3 months and 31.4 months, respectively, which were significantly higher than those of patients carrying other mutations at 11.2 months. Subgroup analysis showed that TTF and OS benefits were observed in female patients, patients without brain metastasis, and patients with good performance status who harbored the G719X mutation.

Conclusion: Patients with the EGFR-G719X mutation achieve significantly better TTF and OS benefits than those with other uncommon EGFR mutations.