Expert review of respiratory medicine最新文献

Introduction: Multifocal lung adenocarcinoma (MFLA) is becoming increasingly recognized as a distinct subset of lung cancer, with unique biology, disease course, and treatment outcomes. While definitions remain controversial, MFLA is characterized by the development and concurrent presence of multiple independent (non-metastatic) lesions on the lung adenocarcinoma spectrum. Disease progression typically follows an indolent course measured in years, with a lower propensity for nodal and distant metastases than other more common forms of non-small cell lung cancer.

Areas covered: Traditional imaging and histopathological analyses of tumor biopsies are frequently unable to fully characterize the disease, prompting interest in molecular diagnosis. We highlight some of the key questions in the field, including accurate definitions to identify and stage MLFA, molecular tests to stratify patients and treatment decisions, and the lack of clinical trial data to delineate best management for this poorly understood subset of lung cancer patients. We review the existing literature and progress toward a genomic diagnosis for this unique disease entity.

Expert opinion: Multifocal lung adenocarcinoma behaves differently than other forms of non-small cell lung cancer. Progress in molecular diagnosis may enhance potential for accurate definition, diagnosis, and optimizing treatment approach.

Introduction: Since early in the HIV epidemic, emphysema has been identified among people with HIV (PWH) and has been associated with increased mortality. Smoking cessation is key to risk reduction. Health maintenance for PWH and emphysema should ensure appropriate vaccination and lung cancer screening. Treatment should adhere to inhaler guidelines for the general population, but inhaled corticosteroid (ICS) should be used with caution. Frontiers in treatment include targeted therapeutics. Major knowledge gaps exist in the epidemiology of and optimal care for PWH and emphysema, particularly in low and middle-income countries (LMIC).

Areas covered: Topics addressed include risk factors, pathogenesis, current treatment and prevention strategies, and frontiers in research.

Expert opinion: There are limited data on the epidemiology of emphysema in LMIC, where more than 90% of deaths from COPD occur and where the morbidity of HIV is most heavily concentrated. The population of PWH is aging, and age-related co-morbidities such as emphysema will only increase in salience. Over the next 5 years, the authors anticipate novel trials of targeted therapy for emphysema specific to PWH, and we anticipate a growing body of evidence to inform optimal clinical care for lung health among PWH in LMIC.

Introduction: Radial probe endobronchial ultrasound (rEBUS) improves the diagnostic yield of peripheral pulmonary lesions (PPLs). A notable methodological limitation of rEBUS is that it does not provide real-time images during transbronchial biopsy (TBB) procedures. To overcome this limitation, a guide sheath (GS) method was developed.

Areas covered: This review covers the procedures and complications of rEBUS-guided TBB with a GS (EGS method). We also present the data from key randomized controlled trials (RCTs) of the EGS method and summarize the usefulness of combining the EGS method with various techniques. Finally, we discuss in which situations EGS should be used.

Expert opinion: A large RCT showed that the diagnostic yield of the EGS method for PPLs was significantly higher than that of rEBUS-guided TBB without a GS (non-GS method). However, since the EGS and non-GS methods each have their own advantages and disadvantages, they should be considered complementary and used flexibly in different cases. In some cases, a combination of the two may be an option. The appropriate combination of EGS with various techniques may enhance the diagnostic yield of PPLs and help prevent complications. The choice should be based on the location and texture of the target lesion, as well as operator skill, resource availability, safety, and accuracy.

Background: Diagnosis of pleural tuberculosis (TB) is tedious owing to its close resemblance with malignant pleural effusion and sparse bacterial load in clinical specimens. There is an immediate need to design a rapid and dependable diagnostic test to prevent unnecessary morbidity/mortality.

Research design and methods: A multi-targeted loop-mediated isothermal amplification (MT-LAMP) was deliberated using mpt64 and IS6110 to diagnose pleural TB within pleural fluids/biopsies. MT-LAMP products were analyzed by gel-based and visual detection methods, viz. SYBR Green I, SYBR Green I+deoxyuridine triphosphate uracil-N-glycosylase (dUTP-UNG), and dry methyl green reactions.

Results: In a pilot study, while assessing pleural TB/non-TB control subjects (n = 40), both SYBR Green I+dUTP-UNG/gel-based MT-LAMP assays exhibited better sensitivity/specificity than SYBR Green I and dry methyl green MT-LAMP. Since it is facile to work with SYBR Green I+dUTP-UNG than gel-based MT-LAMP, we validated the performance of SYBR Green I+dUTP-UNG in a higher number of specimens (n = 97), which revealed somewhat higher sensitivity (85.2 vs. 81.5%) and specificity (97.7 vs. 90.7%) than SYBR Green I MT-LAMP. Furthermore, the sensitivity attained by SYBR Green I+dUTP-UNG MT-LAMP was significantly higher (p < 0.001) than GeneXpert.

Conclusions: Our SYBR Green I+dUTP-UNG MT-LAMP is a simple and reliable method to diagnose pleural TB, which may translate into a point-of-care test.

Introduction: Immune-checkpoint inhibitors (IO) have significantly improved outcomes of patients with non-oncogene-addicted non-small cell lung cancer (NSCLC), becoming the first-line agents for advanced disease. However, resistance remains a significant clinical challenge, limiting their effectiveness.

Areas covered: Hereby, we addressed standard and innovative therapeutic approaches for NSCLC patients experiencing progression after IO treatment, discussing the emerging resistance mechanisms and the ongoing efforts to overcome them. In order to provide a complete overview of the matter, we performed a comprehensive literature search across prominent databases, including PubMed, EMBASE (Excerpta Medica dataBASE), and the Cochrane Library, and a research of the main ongoing studies on clinicaltrials.gov.

Expert opinion: The dynamics of progression to IO, especially in terms of time to treatment failure and burden of progressive disease, should guide the best subsequent management, together with patient clinical conditions. Long-responders to IO might benefit from continuation of IO beyond-progression, in combination with other treatments. Patients who experience early progression should be treated with salvage CT in case of preserved clinical conditions. Finally, patients who respond to IO for a considerable timeframe and who later present oligo-progression could be treated with a multimodal approach in order to maximize the benefit of immunotherapy.

Background: Extracorporeal membrane oxygenation (ECMO) has been used extensively for H1N1 influenza and coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) to improve gas exchange and quickly correct hypoxemia and hypercapnia. This systematic review summarized the evidence on ECMO for the treatment of COVID-19 and influenza-associated ARDS.

Research design and methods: This is a systematic review and meta-analysis of studies to compare the efficacy and safety of ECMO with conventional mechanical ventilation in adults with COVID-19 and influenza-associated ARDS. The study performed a structured search on PubMed, Embase, Web of Science, Scopus and The Cochrane Library. The primary outcome was hospital mortality.

Results: The study included 15 observational studies with 5239 patients with COVID-19 and influenza-associated ARDS. The use of ECMO significantly reduced in-hospital mortality in COVID-19-associated ARDS (OR = 0.40; 95% CI = 0.27-0.58; P < 0.00001) but did not reduce influenza-related mortality (OR = 1.08; 95% CI = 0.41-2.87; P = 0.87). Moreover, ECMO treatment meaningfully increased the incidence of bleeding complications (OR = 7.66; 95% CI = 2.47-23.72; P = 0.0004).

Conclusion: The use of ECMO significantly reduced in-hospital mortality in COVID-19- associated ARDS, which may be related to the advances in ECMO-related techniques and the increased experience of clinicians. However, the incidence of bleeding complications remains high. [Figure: see text].

Introduction: There is increasing evidence that also children can develop Long Covid. However, there are no specific reviews providing a clear description of reported respiratory symptoms and potential diagnostics.

Areas covered: We performed on PubMed a systematic search of studies conducted on children aged less than 18 years with previous SARS-CoV-2 infection complaining about persistent respiratory symptoms; the aim of our review is to characterize the incidence, pattern and duration of respiratory symptoms after the acute infection in pediatric population.

Expert opinion: Children can develop persisting respiratory symptoms, as documented by several follow-up studies both including or not control groups of non-infected children. However, the methodological variabilities of the analyzed studies does not allow to provide firm conclusions about the rate, type and best diagnostics for children with persistent respiratory symptoms. Future studies should investigate on larger pediatric cohorts the role of noninvasive diagnostics and new biomarkers as well as investigating therapeutic options both during acute infection or when Long Covid has been diagnosed.

Introduction: Persistent air leaks (PAL) represent a challenging clinical problem for which there is not a clear consensus to guide optimal management. PAL is associated with significant morbidity, mortality, and increased length of hospital stay. There are a variety of surgical and non-surgical management options available.

Areas covered: This narrative review describes the current evidence for PAL management including surgical approach, autologous blood patch pleurodesis, chemical pleurodesis, endobronchial valves, and one-way valves. Additionally, emerging topics such as drainage-dependent air leak and intensive care unit management are described.

Expert opinion: There has been considerable progress in understanding the pathophysiology of PAL and growing evidence to support the various non-surgical treatment modalities. Increased recognition of drainage-dependent persistent air leaks offers the opportunity to decrease the number of patients requiring additional invasive treatment. Randomized control trials are needed to guide optimal management.

Introduction: Although very uncommon, severe injury and death can occur during scuba diving. One of the main causes of scuba diving fatalities is pulmonary barotrauma due to significant changes in ambient pressure. Pathology of the lung parenchyma, such as cystic lesions, might increase the risk of pulmonary barotrauma.

Areas covered: Birt-Hogg-Dubé syndrome (BHD), caused by pathogenic variants in the FLCN gene, is characterized by skin fibrofolliculomas, an increased risk of renal cell carcinoma, multiple lung cysts and spontaneous pneumothorax. Given the pulmonary involvement, in some countries patients with BHD are generally recommended to avoid scuba diving, although evidence-based guidelines are lacking. We aim to provide recommendations on scuba diving for patients with BHD, based on a survey of literature on pulmonary cysts and pulmonary barotrauma in scuba diving.

Expert opinion: In our opinion, although the absolute risks are likely to be low, caution is warranted. Given the relative paucity of literature and the potential fatal outcome, patients with BHD with a strong desire for scuba diving should be informed of the potential risks in a personal assessment. If available a diving physician should be consulted, and a low radiation dose chest computed tomography (CT)-scan to assess pulmonary lesions could be considered.

Introduction: Preschool wheeze (PSW) is a significant public health issue, with a high presentation rate to emergency departments, recurrent symptoms, and severe exacerbations. A heterogenous condition, PSW comprises several phenotypes that may relate to a range of pathobiological mechanisms. However, treating PSW remains largely generalized to inhaled corticosteroids and a short acting beta agonist, guided by symptom-based labels that often do not reflect underlying pathways of disease.

Areas covered: We review the observable features and characteristics used to ascribe phenotypes in children with PSW and available pathobiological evidence to identify possible endotypes. These are considered in the context of treatment options and future research directions. The role of machine learning (ML) and modern analytical techniques to identify patterns of disease that distinguish phenotypes is also explored.

Expert opinion: Distinct clusters (phenotypes) of severe PSW are characterized by different underlying mechanisms, some shared and some unique. ML-based methodologies applied to clinical, biomarker, and environmental data can help design tools to differentiate children with PSW that continues into adulthood, from those in whom wheezing resolves, identifying mechanisms underpinning persistence and resolution. This may help identify novel therapeutic targets, inform mechanistic studies, and serve as a foundation for stratification in future interventional therapeutic trials.