Seminars in respiratory and critical care medicine最新文献

Respiratory infections are associated with a huge burden of disease every year and disproportionately affect older adults, namely those aged 65 years and older. Older adults are at increased risk of infections compared with their younger counterparts, and once infected, have a higher risk of experiencing severe disease course, complications, and long-term sequelae. Therefore, vaccination is clearly a key strategy to prevent infection and its attendant negative consequences. We review here the burden of common respiratory diseases in older adults, namely influenza, pneumococcal disease, and respiratory syncytial virus. We then review some of the challenges facing immunization of older adults, namely immunosenescence, inflammaging, and low vaccine uptake. Next, potential opportunities for overcoming these challenges are reviewed, including the use of higher antigen doses and/or adjuvants in vaccine formulations for older adults, and the potential of multiomics analyses to improve development, performance, and implementation of vaccines.

In this review, we present the efforts made so far in developing effective solutions to prevent infections caused by seven major respiratory pathogens: influenza virus, respiratory syncytial virus (RSV), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Bordetella pertussis, Streptococcus pneumoniae (pneumococcus), Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Advancements driven by the recent coronavirus disease 2019 (COVID-19) crisis have largely focused on viruses, but effective prophylactic solutions for bacterial pathogens are also needed, especially in light of the antimicrobial resistance (AMR) phenomenon. Here, we discuss various innovative key technologies that can help address this critical need, such as (a) the development of Lung-on-Chip ex vivo models to gain a better understanding of the pathogenesis process and the host-microbe interactions; (b) a more thorough investigation of the mechanisms behind mucosal immunity as the first line of defense against pathogens; (c) the identification of correlates of protection (CoPs) which, in conjunction with the Reverse Vaccinology 2.0 approach, can push a more rational and targeted design of vaccines. By focusing on these critical areas, we expect substantial progress in the development of new vaccines against respiratory bacterial pathogens, thereby enhancing global health protection in the framework of the increasingly concerning AMR emergence.

Pulmonary embolism (PE) and obstructive sleep apnea (OSA) remain a major health issue worldwide with potential overlapping pathophysiological mechanisms. PE, the most severe form of venous thromboembolism, is associated with high morbidity and mortality, presenting challenges in management and prevention, especially in high-risk populations. OSA is a prevalent condition characterized by repeated episodes of upper airway closure resulting in intermittent hypoxia and sleep fragmentation. Although the understanding of epidemiological and pathogenic relationships between OSA and PE is still limited, current data suggest that interactions between these two conditions appear to be relevant. OSA is emerging as a novel risk factor for PE, potentially affecting all components of Virchow's triad: hypercoagulability, endothelial dysfunction, and venous stasis. Epidemiological studies indicate a high prevalence of undiagnosed OSA in acute PE patients. Moderate-to-severe OSA has been linked to worse clinical presentations and outcomes. Furthermore, OSA has been associated with increased risks of PE recurrence and mortality. Future research directions should include clarifying the bidirectional relationship between these conditions and evaluating the effectiveness and safety of continuous positive airway pressure (CPAP) therapy in improving outcomes in patients with concurrent acute PE and OSA.

Lower respiratory tract infection (LRTI) is a major cause of neonatal morbidity and mortality worldwide. Maternal vaccination is an effective strategy in protecting young infants from LRTI, particularly in the first few months after birth when infant is most vulnerable, and most primary childhood vaccinations have not been administered. Additionally, maternal vaccination protects the mother from illness during pregnancy and the postnatal period, and the developing fetus from adverse outcomes such as stillbirth and prematurity. In this paper, we review the safety, efficacy, and effectiveness of maternal vaccines against LRTIs, such as pertussis, influenza, coronavirus disease 2019, and respiratory syncytial virus.

Neuromuscular disorders can cause respiratory impairment by affecting the muscle fibers, neuromuscular junction, or innervation of respiratory muscles, leading to significant morbidity and mortality. Over the past few years, new disease-modifying therapies have been developed and made available for treating different neuromuscular disorders. Some of these therapies have remarkable effectiveness, resulting in the prevention and reduction of respiratory complications. For myasthenia gravis (MG), efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan have been Food and Drug Administration (FDA)-approved for the treatment of acetylcholine receptor (AChR) antibody-positive generalized MG in the past 2 years. Rozanolixiumab is also approved for treating MG caused by muscle-specific tyrosine kinase (MuSK) antibodies. The new MG therapeutics target the complement system or block the neonatal fragment crystallizable (Fc) receptors (FcRn), leading to significant clinical improvement. For spinal muscular atrophy (SMA), nusinersen (intrathecal route) and risdiplam (oral route) modify the splicing of the SMN2 gene, increasing the production of normal survival motor neuron (SMN) protein. Onasemnogene abeparvovec is a gene replacement therapy that encodes a functional SMN protein. All SMA medications, particularly onasemnogene abeparvovec, have led to clinically meaningful improvement. For late-onset Pompe disease (LOPD), avalglucosidase alfa has shown a greater improvement in respiratory function, ambulation, and functional outcomes in comparison to alglucosidase alfa, and cipaglucosidase alfa combined with miglustat has shown improvement in respiratory and motor function in a cohort of enzyme replacement therapy-experienced LOPD patients. Amyotrophic lateral sclerosis (ALS) remains a challenge. The two most recent FDA-approved medications, namely sodium phenylbutyrate and tofersen, may slow down the disease by a few months in a selected population but do not stop the progression of the disease.

Aspiration represents the passage of oropharyngeal content to the lower respiratory tract. The interplay between the host and the aspirate proprieties determines the subsequent aspiration syndrome. A low pH, typical of gastric aspirate, favors chemical pneumonitis, whereas an increased bacterial inoculum causes aspiration pneumonia. About a quarter of patients with aspiration pneumonitis will develop a bacterial superinfection during the course of recovery. While antibiotic therapy is indicated for aspiration pneumonia, supportive care remains the cornerstone of treatment in aspiration pneumonitis. However, the overlapping clinical features of these syndromes lead to initiation of antimicrobial therapy in most cases of aspiration. Bronchoscopy can aid in clinical decision-making by direct airway visualization and also by providing access to a series of emerging biomarkers. Invasive microbiological studies increase diagnostic yield and enable a tailored antibiotic treatment. In conjunction with stewardship programs, invasive sampling and novel molecular diagnostics can decrease the amount of inappropriate antibiotic therapy. In the context of foreign body aspiration, bronchoscopy represents both diagnostic and treatment gold standard.

Therapeutic considerations for aspiration pneumonia prioritize the risk of multidrug-resistant organisms. This involves integrating microbiological insights with each patient's unique risk profile, including the location at the time of aspiration, and whether it occurred in or out of the hospital. Our understanding of the microbiology of aspiration pneumonia has also evolved, leading to a reassessment of anaerobic bacteria as the primary pathogens. Emerging research shows a predominance of aerobic pathogens, in both community and hospital-acquired cases. This shift challenges the routine use of broad-spectrum antibiotics targeting anaerobes, which can contribute to antibiotic resistance and complications such as Clostridium difficile infections-concerns that are especially relevant given the growing issue of antimicrobial resistance. Adopting a comprehensive, patient-specific approach that incorporates these insights can optimize antibiotic selection, improve treatment outcomes, and reduce the risk of resistance and adverse effects.

Aspiration pneumonia refers to the process of alveolar inflammation induced by the inhalation of oropharyngeal secretions into the lower respiratory tract. Predisposing factors comprise swallowing dysfunction, impaired cough reflex, and degenerative neurological diseases. Accumulating evidence projects a fading contribution of anaerobic bacteria in aspiration pneumonia at the expense of Gram-negative bacilli, with Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, becoming the predominant organisms recovered from respiratory specimens. Aspiration of oropharyngeal secretions colonized with respiratory pathogens induces a profound disequilibrium of the lung microbiota resulting in a state of dysbiosis. Understanding this complex temporal variability between microbiome-host associations was only made possible with the introduction of metagenomic sequencing. In this narrative review, we summarize existing knowledge and elaborate on the evolving microbiology of aspiration pneumonia including the link between oral microbiome and pulmonary aspiration. We also highlight the progress and challenges in instituting microbiome-targeted strategies for preventing and treating the sequelae of aspiration pneumonia.

Aspiration pneumonia is a clinical entity with important ethical considerations. It is imperative for clinicians to understand these considerations to best provide counsel to patients and their families, allowing them to make fully informed decisions. Given that aspiration pneumonia is frequently associated with end of life, there are palliative medicine principles that may help in the treatment of this disease.

Aspiration following anesthesia is a major patient issue and a difficulty for anesthesiologists. Aspiration syndromes are more common than anticipated, and the condition is frequently undetected. Clinical signs are often dictated by the characteristics of aspiration, such as the infectivity of the material, its volume, and the severity of the underlying clinical condition. Pulmonary aspiration can cause an acute or persistent inflammatory response in the lungs and upper airways that can be complicated by tracheobronchitis, aspiration pneumonia, aspiration pneumonitis, acute respiratory distress syndrome, and subsequent bacterial infection due to particle, acid, and bacteria-related processes. Aspiration during anesthesia, while relatively rare, poses significant risks for patient morbidity and mortality. Chemical and bacterial aspiration provide distinct diagnostic and management issues. Preventive strategies such as a complete preoperative risk assessment, adherence to fasting rules, proper patient positioning, and the use of protective airway devices are critical in reducing aspiration risk. In addition, drugs such as proton pump inhibitors can help lower stomach acidity and volume. Innovations in monitoring techniques, better training, and awareness activities are critical to enhancing aspiration event management. Given the importance of this entity, this narrative review sought to make an updated overview of the management of aspiration after anesthesia: chemical versus bacterial, differential diagnosis, management, and prevention.