Therapeutic Advances in Respiratory Disease最新文献

{"title":"Efficacy and safety of ensifentrine in treatment of COPD: a systematic review and meta-analysis of clinical trials.","authors":"Bara M Hammadeh, Osama M Younis, Muaath I Alsufi, Muhammad Idrees, Ayham Mohammad Hussein, Abdullah Yousef Aldalati, Fares A Qtaishat, Banan Qatawneh, Al Bugazia, Raed A Hamed","doi":"10.1177/17534666251347775","DOIUrl":"10.1177/17534666251347775","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a progressive lung disease marked by airway inflammation and obstruction. Ensifentrine is a novel inhaled PDE3 and PDE4 inhibitor with both bronchodilator and anti-inflammatory effects.</p><p><strong>Objectives: </strong>Comprehensively review the available evidence on ensifentrine and its potential role in COPD management.</p><p><strong>Design: </strong>Systematic review and meta-analysis with trial sequential analysis of randomized clinical trials.</p><p><strong>Data sources and methods: </strong>We systematically searched PubMed, Scopus, ScienceDirect, Cochrane Library, and Medline for clinical trials published between 2018 and August 2024 that evaluated the safety and efficacy of ensifentrine in patients with COPD. We assessed study quality using the RoB 2 tool and conducted the meta-analysis with the \"meta\" package in R (version 4.3.2), using the mean difference with a 95% confidence interval to evaluate changes in outcomes.</p><p><strong>Results: </strong>Five studies met the predefined inclusion criteria with 2519 participants. At week 12, the pooled analysis indicated that forced expiratory volume in 1 s (FEV₁) and trough FEV₁ were significantly increased in the ensifentrine group (mean difference (MD): 91.32; 95% CI: 69.63 to 113.01) and (MD: 40.90; 95% CI: 19.65 to 62.15), respectively. At week 24, the pooled analysis indicated that the evaluating respiratory symptoms total score was significantly decreased in the ensifentrine group (MD: -0.81; 95% CI: -1.36 to -0.27), transition dyspnea index score was significantly increased in the ensifentrine group (MD: 0.96; 95% CI: 0.62 to 1.29), no significant difference was observed in rescue medication use (MD: -0.30; 95% CI: -0.60 to 0.00), and no significant difference was observed in St. George's Respiratory Questionnaire total score (MD: -1.46; 95% CI: -3.22 to 0.30). Based on subgroup analysis, higher doses were associated with more favorable results.</p><p><strong>Conclusion: </strong>In conclusion, owing to its dual effects, ensifentrine has a significant impact on improving pulmonary function and quality of life with minimal side effects. Promising results are expected if implied by synergizing with other drugs, however, more studies are needed to study the long-term effect on disease progression.</p><p><strong>Trial registration: </strong>The study protocol was published via PROSPERO: International Prospective Register of Systematic Reviews (#CRD42024570799).</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251347775"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in genetic characteristics between Chinese and non-Chinese patients with pulmonary alveolar microlithiasis-case series and a systematic review.","authors":"Mengyao Guo, Lijuan Hua, Wenxue Bai, Xuezhao Wang, Dongyuan Wang, Lirong Chen, Bingyi Liu, Min Xie","doi":"10.1177/17534666251381679","DOIUrl":"10.1177/17534666251381679","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disorder caused by <i>SLC34A2</i> variants, characterized by diffuse alveolar calcium phosphate deposits. While the <i>SLC34A2</i> mutation spectrum has been well-documented, the distinct variant landscape in Chinese patients remains unclear.</p><p><strong>Objectives: </strong>This study aims to report three newly identified PAM cases and describe the <i>SLC34A2</i> mutation spectrum of Chinese PAM patients through a systematic review.</p><p><strong>Design: </strong>We documented the diagnosis and treatment processes and genetic variations of three PAM cases for reporting. Furthermore, we searched academic websites for published PAM cases with <i>SLC34A2</i> variants and extracted clinical and genetic data for analysis.</p><p><strong>Methods: </strong>We employed whole-exome sequencing to identify genetic mutations of these three patients. We systematically searched PubMed, Web of Science, China National Knowledge Infrastructure, and Cochrane Library for published PAM cases with <i>SLC34A2</i> mutations. Clinical and genetic data were extracted into an Excel database and analyzed using SPSS 23.0 software (IBM, Armonk, NY, USA).</p><p><strong>Results: </strong>Among the three cases we reported, two homozygous mutations in <i>SLC34A2</i>-c.910A>T (p.Lys304*) in exon 8 and c.575C>A (p.Thr192Lys) in exon 6 were identified. Analysis of 27 Chinese and 49 non-Chinese PAM patients revealed similar clinical manifestations, but a strikingly distinct genetic spectrum. Compound heterozygous mutations predominated in Chinese patients, while only two cases of compound heterozygous mutations were found in non-Chinese patients. Deletion/insertion mutations are the most common in non-Chinese patients (19/47, 40.4%), whereas nonsense mutations are the most frequent in Chinese patients (12/20, 60%). Further analysis of the reported <i>SLC34A2</i> mutation sites in Chinese PAM patients showed hotspot regions in exons 5, 6, and 8, with c.910A>T in exon 8 being a unique gene screening target in Chinese patients.</p><p><strong>Conclusion: </strong>This study delineates a distinct spectrum of <i>SLC34A2</i> mutations in Chinese PAM patients, highlighting the importance of ethnicity-specific genetic screening in PAM diagnosis.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251381679"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of statins on pulmonary function in patients with persistent hyperlipidemia: a retrospective cohort study.","authors":"Hsiao-Chin Shen, Che-Hao Tseng, Yi-Hsuan Lin, Hsiao-Yun Yeh, Hung-Cheng Tsai, Shiao-Ya Hong, Tzu-Hao Li, Chien-Wei Su, Diahn-Warng Perng, Ying-Ying Yang, Ming-Chih Hou","doi":"10.1177/17534666251320875","DOIUrl":"10.1177/17534666251320875","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary function tests offer crucial parameters for evaluating lung health and predicting clinical outcomes. Hyperlipidemia, a prevalent metabolic disorder, has been linked to declining pulmonary function. Statins are an essential therapy for lowering lipid levels in hyperlipidemia.</p><p><strong>Objectives: </strong>This study aims to investigate the therapeutic potential of statins in mitigating the decline in pulmonary function.</p><p><strong>Design: </strong>This is a retrospective cohort study.</p><p><strong>Methods: </strong>Out of 8286 patients who underwent spirometry testing from January 2018 to December 2020, 492 patients were included in the final analysis. The relationship between statin usage, dosage, along with other biometric indices and spirometry parameters were evaluated. Multivariate logistic regression analyses were employed to assess the association between statin use and the decline in pulmonary function.</p><p><strong>Results: </strong>In patients with persistent hyperlipidemia, the use of statins was associated with a higher predicted percentage of forced expiratory volume in 1 second (FEV1) compared to non-users (84.0% vs 78.0%, <i>p</i> = 0.015). Logistic regression models further revealed that statin use independently prevented FEV1 decline, irrespective of dosage (adjusted OR 0.036, 95% CI: 0.002-0.618 in lower statins dose group and adjusted OR 0.170, 95% CI: 0.019-1.552 in higher statins dose group).</p><p><strong>Conclusion: </strong>The findings suggested that statin usage, regardless of dosage, independently mitigated the decline in pulmonary function among patients with persistent hyperlipidemia. Early initiation of statin therapy may hold promise for individuals experiencing hyperlipidemia and declining pulmonary function.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251320875"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors for spontaneous pleurodesis in patients with indwelling pleural catheters for malignant pleural effusion: a safety net hospital experience.","authors":"Saad Farooq, Sabiha Armin, Jordan E Killingsworth, Akriti Agrawal, Adishwar Rao, Rosa M Estrada-Y-Martin, Sujith V Cherian","doi":"10.1177/17534666251318844","DOIUrl":"10.1177/17534666251318844","url":null,"abstract":"<p><strong>Background: </strong>Malignant pleural effusion (MPE) affects approximately 150,000 patients in the United States each year and usually signifies advanced-stage cancer. The optimal treatment remains a challenge but indwelling pleural catheters (IPC) offer several advantages and may help achieve spontaneous pleurodesis (SP) in some patients.</p><p><strong>Objectives: </strong>We aim to investigate the predictors of SP among patients with MPE, particularly in a resource-limited community-based safety net hospital.</p><p><strong>Design: </strong>This is a retrospective cohort study done at a community-based safety net hospital.</p><p><strong>Methods: </strong>Adults diagnosed with or suspected of having MPE between January 2015 and December 2023 who underwent IPC placement were included. Data was collected retrospectively from December 2023 to June 2024. Data encompassed demographics, imaging, post-procedural complications, pleural fluid analysis, oncology treatment history, and utilization of medical thoracoscopy without chemical pleurodesis (MTWCP) for diagnosis.</p><p><strong>Results: </strong>A total of 173 patients underwent IPC insertion. Most of our patients were women (64.2%), and Latin American (65.9%), with a mean age of 55.3 years. The most common type of primary cancer was breast (28.9%) followed by lung (23.1%) and lymphoma (6.9%). Pleural fluid characteristics such as glucose, eosinophils, Lactate Dehydrogenase (LDH), and protein concentration were not significantly associated with SP. Most patients had low Eastern Cooperative Oncology Group scores of 0-2 (64.6%) and low LENT (Lactate Dehydrogenase (L), Eastern Cooperative Oncology Group (E) Performance Score, Neutrophil-to-Lymphocyte Ratio (N), and Tumor type (T) score) scores of 0-4 (59%). Lower scores (better functional status) were significantly associated with SP. Post-IPC chemotherapy and/or radiotherapy and immunotherapy were significantly associated with SP, adjusted odds ratio (OR) 7.295 (95% CI: 3.05-17.4, <i>p</i> = 0.001) and adjusted OR 6.261 (95% CI: 2.73-14.36, <i>p</i> = 0.001) respectively. MTWCP was also a predictor of SP with an adjusted OR of 4.031 (95% CI: 1.452-11.19, <i>p</i> = 0.007).</p><p><strong>Conclusion: </strong>Our study is the first to assess predictors of SP in a resource-limited safety net hospital representing under-represented and underserved patients. We identify several factors associated with higher rates of SP such as higher functional status, MTWCP, chemotherapy, immunotherapy, and radiation post-IPC placement. The study findings can help clinicians consider IPC placement and guide them regarding the duration and possible complications of IPC. MTWCP appears to improve the success of SP. Further studies are needed to assess these findings further.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251318844"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystic fibrosis: new challenges and perspectives beyond elexacaftor/tezacaftor/ivacaftor.","authors":"Vito Terlizzi, Miquéias Lopes-Pacheco","doi":"10.1177/17534666251323194","DOIUrl":"10.1177/17534666251323194","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251323194"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cohort multiple randomized controlled trial in pediatric asthma to assess the long- and short-term effects of eHealth interventions: protocol of the CIRCUS study.","authors":"Tamara Ruuls, Romi Sprengers, Vera Hengeveld, Boony Thio, Monique Tabak, Deborah Zagers, Job van der Palen, Mattiènne van der Kamp","doi":"10.1177/17534666251323192","DOIUrl":"10.1177/17534666251323192","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>The CIRCUS study design is a cohort multiple randomized controlled trial (cmRCT) with a dynamic cohort of 300 pediatric asthma patients.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>This study was ethically approved by the Medical Research Ethics Committee (NL85668.100.23) on February 15th, 2024.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.<b><i>Trial registration</i>:</b> The protocol is registered at ClinicalTrials.gov (NCT06278662).</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251323192"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CodeX effectively identifies high-risk patients with asthma or COPD in Dutch primary care, supporting guideline-driven treatment.","authors":"Iris van Geer-Postmus, Marika T Leving, Yoran H Gerritsma, Esmé Baan, Lars Dijk, Evelien Harms, David Price, Gerian H Prins, Jennifer K Quint, Dermot Ryan, Philippe Salomé, Björn Ställberg, Nilouq Stoker, Janwillem H Kocks","doi":"10.1177/17534666251329192","DOIUrl":"10.1177/17534666251329192","url":null,"abstract":"<p><strong>Background: </strong>Prevention of lung attacks (LAs)/exacerbation is an important treatment goal in both asthma and chronic obstructive pulmonary disease (COPD). However, LAs are often not registered as such in medical records.</p><p><strong>Objectives: </strong>Development and evaluation of CodeX Asthma and COPD.</p><p><strong>Design: </strong>An electronic medical record-based algorithm to identify LAs in Dutch primary care patients with asthma or COPD was developed. The algorithms were evaluated in nine general practices in the Netherlands.</p><p><strong>Results: </strong>A total of 479 LAs (in 1164 patients) were identified with CodeX Asthma in the past year, of which only 16% were registered. CodeX COPD identified 321 LAs (in 242 patients) in the past 3 years, of which two were registered.</p><p><strong>Conclusion: </strong>CodeX algorithms are capable of identifying unrecorded LAs and high-risk/uncontrolled patients in an easy way. This offers primary care providers a simple solution to easily identify and closely manage high-risk patients with asthma or COPD by identifying LAs' frequency and potential under- or overtreatment.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251329192"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of pulmonary hypertension after seven world symposia.","authors":"Rodolfo A Estrada, Sandeep Sahay, Adriano R Tonelli","doi":"10.1177/17534666251342898","DOIUrl":"10.1177/17534666251342898","url":null,"abstract":"<p><p>This review focuses on the advancements in the treatment of pulmonary hypertension (PH), especially after the Food and Drug Administration (FDA) approval of sotatercept and the advances in treatment recommendations after seven World Symposia on PH. PH, a complex and progressive condition defined hemodynamically by a mean pulmonary artery pressure >20 mmHg, encompasses multiple PH groups, each with distinct pathophysiological characteristics and treatment implications. Diagnosing PH can be challenging because symptoms like shortness of breath, fatigue, and chest pain are nonspecific. Contemporary treatment of pulmonary arterial hypertension aims to improve outcomes, symptoms, and overall quality of life, with a primary focus on preventing and treating right ventricular failure. Comprehensive risk stratification remains crucial, aiding in personalized therapy adjustments that improve patients' outcomes. This review also touches upon the limited treatment options for other PH groups, like PH associated with left heart disease, parenchymal lung diseases, and chronic thromboembolic PH, underscoring the need for expanded therapeutic options. Despite advances, challenges remain: diagnostic delays, misdiagnosis, absence of head-to-head clinical trials, and the timing of introducing newer treatments such as sotatercept are discussed, emphasizing an integrated approach that transcends vasodilation to target underlying disease mechanisms. Future directions envision a comprehensive risk stratification incorporating right ventricular function and a mechanism-based treatment paradigm, encouraging a tailored therapeutic approach in PH management.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251342898"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep and breathing in children with Joubert syndrome and a review of other rare congenital hindbrain malformations.","authors":"Jia-Der Ju-Wang, Jennifer C Dempsey, Cristian Zhang, Daniel Doherty, Manisha Witmans, Mary Anne Tablizo, Maida Lynn Chen","doi":"10.1177/17534666241308405","DOIUrl":"10.1177/17534666241308405","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>We conducted a cross-sectional study on a cohort of 109 families affected by JS.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Study participants with JS were older than their unaffected siblings (<i>p</i> = 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 (<i>p</i> < 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666241308405"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Azithromycin and oesophageal motility in chronic respiratory disease: a feasibility study.","authors":"Dominic L Sykes, Kayleigh Brindle, Rohan Menon, Simon P Hart, Jennifer Nielsen, Warren Jackson, John Gallagher, Elisabeth Kirton, Mengru Zhang, Alyn H Morice, Michael G Crooks","doi":"10.1177/17534666251360065","DOIUrl":"10.1177/17534666251360065","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>We assessed the feasibility of performing continuous cough monitoring and repeated high-resolution oesophageal manometry (HROM) in patients with chronic respiratory disease.</p><p><strong>Design: </strong>We conducted an open-label, single-arm, feasibility trial.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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% (<i>n</i> = 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>This trial was prospectively registered ClinicalTrials.gov ID: NCT05469555.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251360065"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}