Current Opinion in Pulmonary Medicine最新文献

Purpose of review: This review summarizes the clinical symptoms of primary ciliary dyskinesia (PCD) beginning at birth and current approaches for confirming diagnosis. Strengths and limitations of innovative adjunctive tests to improve detection are discussed, ultimately highlighting the importance of PCD expert networks to develop standardized guidelines and develop a standalone diagnostic tool.

Recent findings: PCD is underdiagnosed globally, reflecting overall awareness of this disease and limitations of diagnostic approaches. Over 50 disease-causing genes have been characterized, yet more are discovered each year. No single test can detect all PCD cases, therefore further research is needed to improve clinical options for diagnosis.

Summary: PCD is a genetic ciliopathy with serious health complications and impacts on quality of life. Clinical manifestation can vary significantly between individuals, which can delay diagnosis and negatively affect patient outcomes. Current diagnostic tests for PCD require significant resources and training to interpret, and the best-available tests may miss up to 30% of cases. Further work facilitated by expert collaborative networks will be instrumental to develop novel, enhanced diagnostic tools and ultimately improve outcomes for patients.

Purpose of review: Sleep disordered breathing (SDB) encompasses a spectrum of disorders ranging from snoring to complete upper airway collapse and cessation of respiration leading to oxygen desaturation and sleep fragmentation. SDB is highly prevalent in the pregnant population, particularly predisposed to SDB because of physiological changes such as hormonal changes, changes to body habitus, and respiratory mechanics due to the gravid uterus.

Recent findings: The disorder has been associated with adverse maternal outcomes in pregnancy such as gestational hypertension, preeclampsia, impaired glucose metabolism, severe maternal cardiovascular morbidity, and long-term morbidity, as well as maternal mental health conditions with potential societal consequences. There is also mounting evidence on the impact of SDB with regards to the fetal and neonatal outcomes, including preterm birth, altered growth trajectories, and congenital anomalies, as well as evidence of epigenetic changes in the offspring exposed to disordered breathing during sleep.

Summary: This review focuses on SDB in pregnancy and recent data demonstrating its impact on maternal morbidity and fetal and neonatal outcomes, and recent guidelines and data on treatment modalities and their impact on pregnancy health.

Purpose of review: Primary ciliary dyskinesia is a rare, inherited disease, and over 60 genes have been linked to motile ciliopathies. During the past quarter century, our understanding of the complex genetics and biological function of motile cilia has greatly advanced.

Recent findings: Our growing knowledge of genetics and pathophysiology of primary ciliary dyskinesia has yielded insights into novel clinical features and genotype-phenotype relationships in motile ciliopathies. Children with biallelic CCDC39 or CCDC40 mutations have greater lung disease, related to both cilia motility-dependent and motility-independent effects. Pathogenic variants in genes involved in cilia generation, like CCNO , are also associated with more severe lung disease. Conversely, people who have defects in other genes, like DHAH11 and RSPH1 , have less severe lung disease, possibly related to residual ciliary motility. Finally, a growing number of primary ciliopathies are associated with abnormal motile cilia ultrastructure and function, and specific pathogenic variants can lead to distinct clinical presentations, best illustrated by structure-function studies in TUBB4B .

Summary: These findings have yielded new insights into the clinical heterogeneity of motile ciliopathies, thus broadening their clinical spectrum. Additional research to elucidate the underlying pathophysiology in these overlapping conditions is warranted.

Purpose of review: Cystic fibrosis (CF) and non-CF bronchiectasis can predispose patients to airway infections that are difficult to treat. The purpose of this review is to discuss recently developed anti-infectives which show promise in treating these infections.

Recent findings: The microbiology underlying respiratory tract infections in persons with CF (pwCF) and non-CF bronchiectasis is complex. Both traditional and nontraditional anti-infective approaches have recently been discovered and/or are actively being studied for the treatment of airway infections. Traditional antibiotics, including small molecules/compounds/formulations, and nontraditional methods, such as monoclonal antibodies and bacteriophages, have shown promise in their ability to treat airway infections in case studies, case series, and/or clinical trials.

Summary: Several new approaches are currently being developed to better manage airway infections associated with both CF and non-CF bronchiectasis. While many of these new therapies are promising, more studies are needed to assess their safety and efficacy.

Purpose of review: This review highlights the emerging data on the use of incretin therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RA) and dual GLP-1RA and glucose-dependent insulinotropic peptide (GIP) receptor agonists, on the treatment of obstructive sleep apnea (OSA). Given known cardiometabolic and neurocognitive consequences of OSA, optimizing treatment is essential. In the setting of widespread research efforts and clinical implementation of dual agonists in managing OSA, obesity and other cardiometabolic diseases, this review is timely.

Recent findings: Several randomized controlled trials and meta-analyses have shown GLP-1 and GIP receptor agonists to reduce apnea-hypopnea index (AHI) and body weight in patients with OSA. This impact has been demonstrated with the use of pharmacotherapy alone and in combination with traditional positive airway pressure (PAP) therapy. GLP-1RA may positively affect OSA through reducing systemic inflammation and decreasing adiposity, including via hormone changes, delayed gastric emptying, and central mechanisms impacting appetite regulation and sleep-wakefulness.

Summary: Novel pharmacological advances in individuals with OSA and obesity have shown promise in cardiometabolic disease control. Longitudinal follow-up to monitor the efficacy and adverse effects of incretin therapies, and further comparison studies with PAP therapy, are warranted.

Purpose of review: There is a critical need for new therapies addressing the high unmet needs of individuals with rare lung diseases. This review examines the challenges industry sponsors face in developing therapeutic products for rare lung diseases, using cystic fibrosis as an example.

Recent findings: Since the development of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, the drug development landscape for cystic fibrosis has changed. New challenges include defining success in an era of small molecule CFTR modulators, recruitment from a small, ultra-rare population, limited experience with novel trial designs and biomarkers, and fluctuations in funding opportunities.

Summary: While challenges to drug development in rare lung disease, including cystic fibrosis, these challenges also present opportunities for innovation amongst industry sponsors, researchers, foundations/advocacy groups, regulators, and funders. Through collaborative partnerships, we can achieve our collective goal of improving the quality and length of lives of those suffering from rare lung diseases.

Purpose of review: Sleep disordered breathing (SDB) is a direct consequence of tetraplegic spinal cord injury (SCI), is highly prevalent in both tetraplegia and paraplegia, and is associated with worse daytime functioning and reduced quality of life. Despite this, most people with SCI are undiagnosed and untreated for the disorder. This narrative review summarises research from the last 5 years on the epidemiology, pathophysiology, and consequences of SDB in SCI, as well as the current approaches to screening, diagnosis, and treatment of SDB in this population.

Recent findings: Previous research predominantly focussed on SDB in tetraplegia, however recent studies have established that people with paraplegia also experience substantially higher prevalence than the general population. SDB risk screening questionnaires are not helpful because SDB in SCI is so prevalent, and questionnaires alone cannot exclude true negative cases. Alternative treatments, such as mandibular advancement devices, are feasible and likely effective, and alternative care models may improve rates of diagnosis and access to treatments.

Summary: Recent research into SDB in SCI has identified novel, emergent themes, however researchers must collaborate more to achieve sample sizes that can deliver impact in this relatively rare population.

Purpose of review: Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing, with rising prevalence and increasingly recognized for its association with multisystem involvement, particularly abnormalities in glucose metabolism. This review examined the relationship between OSA and glucose metabolism and associated cardiovascular outcomes.

Recent findings: OSA is a significant risk factor for the development of abnormal glucose metabolism and is strongly associated with incident cardiovascular disease, partly mediated by impaired glucose regulation. Emerging evidence highlights a bidirectional relationship between OSA and glucose dysregulation, including insulin resistance and type 2 diabetes. Specific OSA phenotypes such as rapid eye movement (REM)-related OSA and marked nocturnal desaturation have been associated with worsened glycemic control. However, current data show inconsistent improvements in glucose homeostasis following continuous positive airway pressure (CPAP) therapy, indicating the need for more targeted approaches. Meanwhile, weight loss by lifestyle modification, bariatric surgery or medications have been shown to improve OSA as well as glycemic control in people with diabetes.

Summary: Personalized strategies targeting specific OSA phenotypes may improve metabolic outcomes in patients with coexisting glucose dysregulation. Integrating metabolic biomarkers into clinical practice could enable earlier detection of maladaptive changes and support precision-guided interventions to improve long-term outcomes.

Purpose of review: Preventing disease progression is a key element of chronic obstructive pulmonary disease (COPD) management. COPD exacerbations are adverse events that can result in a decline of lung function that can persevere. Therefore, reducing exacerbation frequency has the potential to affect disease progression and improve health status of COPD patients. This narrative review explores monitoring for disease progression in COPD and its potential association with COPD exacerbations.

Recent findings: Pharmacotherapy can slow down disease progression, but the effect is mediated only in part by reducing exacerbations. While disease progression is continuous, patients with established airflow obstruction in early stages appear more vulnerable to faster declines in lung function. Longitudinal monitoring of lung function and structure is necessary to identify patients with disease progression.

Summary: Pharmacotherapy is an effective option for preventing disease progression. A holistic approach including longitudinal pulmonary function testing, clinical symptoms and imaging may be necessary to detect disease progression for early intervention.