SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE

Bacteriology of Aspiration Pneumonia: The Lung Microbiome and the Changing Microbial Etiology
Fadell F, Saliba R and El-Solh AA
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 , , and , 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.
Imaging of Aspiration: When to Suspect Based on Imaging of Bacterial Aspiration, Chemical Aspiration, and Foreign Body Aspiration
Agarwala P, Machnicki S, Ryu JH, Hu X, Saez K and Raoof S
Aspiration-related syndromes comprise a broad spectrum of diseases affecting the airways and lung parenchyma resulting from inadvertent entry of oropharyngeal or gastric contents into the respiratory tract. The diagnosis can be challenging given lack of self-reported symptoms and unwitnessed or silent aspiration events. Aspiration is a common finding in healthy individuals suggesting that host defenses play a critical role in the pathophysiology. In the absence of strict criterion, a high index of suspicion is necessary based on recognition of established risk factors and identification of characteristic imaging findings. Conditions predisposing to altered levels of consciousness and neuromuscular weakness can lead to dysphagia, impaired cough reflux, and subsequent aspiration. The most salient feature on imaging is the anatomic location of the abnormalities, with the superior segments of the lower lobes and posterior segments of upper lobes involved in the recumbent position, and basilar segments of lower lobes in the upright position. Acute syndromes include pneumonia, pneumonitis, and foreign body aspiration. In the more indolent form of aspiration, bronchiectasis, diffuse bronchiolitis, and interstitial lung disease can develop. A detailed understanding of associated radiographic findings for these syndromes can help to implicate aspiration as the cause for imaging abnormalities and ultimately optimize patient management.
"SWALLOWING AND ASPIRATION: HOW TO EVALUATE AND TREAT SWALLOWING DISORDERS ASSOCIATED WITH ASPIRATION PNEUMONIA IN OLDER PERSONS"
Ortega O, Guidotti L, Yoshimatsu Y, Sitges C, Martos J, Miró J, Martín A, Amadó C and Clavé P
BACKGROUND Aspiration pneumonia (AP) is the most severe complication of oropharyngeal dysphagia (OD). It is highly underdiagnosed and undertreated among older patients hospitalized with community-acquired pneumonia (CAP). Our aim is to review the state of the art in the diagnosis and treatment of swallowing disorders associated with AP. METHODOLOGY We performed a narrative review, including our experience with prior studies at Hospital de Mataró, on the diagnosis and treatment of AP. RESULTS AP refers to pneumonia occurring in patients with swallowing disorders, frequently coinciding with poor oral health and vulnerability. Its main risk factors include oropharyngeal aspiration, impaired health status, malnutrition, frailty, immune dysfunction and oral colonization by respiratory pathogens. Incidence is estimated at between 5%-15% of cases of CAP but it is highly underdiagnosed. Diagnostic criteria for AP have not been standardized but should include its main pathophysiological element, oropharyngeal aspiration. Recently, a clinical algorithm was proposed, based on the recommendations of the Japanese Respiratory Society (JRS), that includes aspiration risk factors and clinical evaluation of OD. To facilitate the task for healthcare professionals, new AI-based screening tools for OD combined with validated clinical methods such as the volume-viscosity swallowing test (V-VST) for the detection of AP are being validated. Prevention and treatment of AP require multimodal interventions aimed to cover the main risk factors: textural adaptation of fluids and diets to avoid oropharyngeal aspiration; nutritional support to avoid malnutrition; and oral hygiene to reduce oral bacterial load. CONCLUSIONS The diagnosis of AP must be based on standardized criteria providing evidence on the main etiological factor, oropharyngeal aspiration. Clinical algorithms are valid in the diagnosis of AP and the identification of its main risk factors. Combination of AI-based tools with V-VST can lead to massive screening of OD and save resources and improve efficiency in the detection AP.
Is There a Role for Bronchoscopy in Aspiration Pneumonia?
Darie AM and Stolz D
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.
The Role of Viral Infections in the Development and Progression of COPD
Burkes R
Chronic obstructive pulmonary disease (COPD) is a common chronic disease seen in smokers associated with poor functional status, quality of life, and morbidity and mortality from acute worsening of chronic symptoms, also called exacerbations. As a disease, the risk factors for COPD are well defined; however, there is room for innovation in identifying underlying biological processes, or "endotypes," that lead to the emergence and/or progression of COPD. Identifying endotypes allows for more thorough understanding of the disease, may reveal the means of disease prevention, and may be leveraged in novel therapeutic approaches. In this review, we discuss the interface of viral infections with both cellular and epithelial immunity as a potential endotype of interest in COPD.
Future Considerations and Areas for Innovation for Pulmonary Rehabilitation in Chronic Obstructive Lung Disease Patients
Connell JW, Humason SA, Panos RJ and Burkes R
Pulmonary rehabilitation is an effective therapy that improves day-to-day symptoms and quality of life in patients with chronic obstructive pulmonary disease. In this review, we look at the role of virtual programs, implementation of artificial intelligence, emerging areas of improvement within the educational components of programs, and the benefit of advanced practice providers in directorship roles.
Medications to Modify Aspiration Risk: Those That Add to Risk and Those That May Reduce Risk
Gonçalves-Pereira J, Mergulhão P and Froes F
Aspiration pneumonia results from the abnormal entry of fluids into the respiratory tract. We present a review of drugs known to affect the risk of aspiration. Drugs that increase the risk of aspiration pneumonia can be broadly divided into those that affect protective reflexes (like cough and swallowing) due to direct or indirect mechanisms, and drugs that facilitate gastric dysbiosis or affect esophageal and intestinal motility. Chief among the first group are benzodiazepines and antipsychotics, while proton pump inhibitors are the most well-studied in the latter group. Pill esophagitis may also exacerbate swallowing dysfunction. On the other hand, some research has also focused on pharmaceutical modulation of the risk of aspiration pneumonia. Angiotensin-converting enzyme inhibitors have been demonstrated to be associated with a decrease in the hazard of aspiration pneumonia in high-risk patients of Chinese or Japanese origin. Drugs like amantadine, nicergoline, or folic acid have shown some promising results in stroke patients, although the available evidence is thus far not enough to allow for any meaningful conclusions. Importantly, antimicrobial prophylaxis has been proven to be ineffective. Focusing on modifiable risk factors for aspiration pneumonia is relevant since this may help to reduce the incidence of this often severe problem. Among these, several commonly used drug classes have been shown to increase the risk of aspiration pneumonia. These drugs should be withheld in the high-risk population whenever possible, alongside general measures, such as the semirecumbent position during sleep and feeding.
Therapy of Aspiration: Out-of-Hospital and In-Hospital-Acquired
Pan D, Isaacs B and Niederman MS
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 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.
Advances in the Understanding and Management of Chronic Obstructive Pulmonary Disease
Burkes R and MacRosty C
Navigating COPD in Aging Populations: Insights Into Pathophysiology and Comprehensive Care
Atchley WT, Montgomery A, Seth R, Gandhi T and Brewer S
Chronic obstructive pulmonary disease (COPD) poses a significant and growing health burden among aging populations, marked by increasing prevalence and complex management challenges specific to elderly patients. This review explores the multifaceted interplay between COPD and aging, highlighting overlapping pathophysiological processes and comorbidities that complicate diagnosis and treatment. We examine age-specific management strategies, emphasizing the need for tailored approaches that account for the unique physical, cognitive, and health-related quality of life impacts on older adults. Additionally, we discuss preventive treatments and the critical roles of mental health, end-of-life care, and caregiver support in comprehensive disease management. The importance of integrative approaches to enhancing health care delivery is also underscored. Finally, we outline future directions, focusing on novel treatment pathways and the identification of biomarkers for early detection. Addressing these elements is essential for optimizing care in this vulnerable population and alleviating the significant societal and economic impacts of COPD among aging patients.
Pulmonary Vascular Disease in Chronic Obstructive Pulmonary Disease
Kay D, Bernardo R and Elwing J
Pulmonary hypertension (PH) is a vascular disease characterized by pulmonary artery remodeling and right heart failure. PH related to COPD is a precapillary form of the disease, with hemodynamic measurements including a mean pulmonary artery pressure of greater than 20 mm Hg, a wedge pressure of less than 15 mm Hg, and a pulmonary vascular resistance of greater than 3 WU (Woods units), categorized under the World Health Organization classification as group 3. The presence of PH in COPD has been known to increase morbidity and mortality. Limited studies have evaluated treatment options for PH related to COPD.
Management of Chronic Neuromuscular Respiratory Failure in the Intensive Care Unit
Ghanem MH, Lee W and Lussier BL
In this seminar we describe the critical care management of patients with chronic neuromuscular diseases (cNMD). Determination of the acuity of the critical illness and trajectory of illness in the setting of cNMD is necessary to guide decision making. Systemic complications of critical illness, cardiac support needs, and peri-intubation considerations may be affected by underlying diagnosis. Mechanical ventilatory support, whether noninvasive or invasive, requires redefinition of the goals of ventilation on a patient-by-patient basis. Mode and approach to invasive ventilation and liberation to noninvasive ventilation versus tracheostomy have limited evidence, but potential clinical approaches are reviewed.
Aspiration after critical illness: role of endotracheal tube, tracheostomy, swallowing disorders
Osorio B, Krakora R, Epping G, Wright D and Rajwani K
Swallowing is a complex process that involves over 50 muscles and nerves and has two critical roles: passing food from the oral cavity through the pharynx and into the esophagus and preventing contents from entering the airway. If a patient's swallowing physiology or airway protective mechanisms are disturbed, the airways and the lungs have innate defense systems to protect against injury and infection. However, critically ill patients are more likely to develop dysphagia, which is an impairment or malfunction in any aspect of the swallowing mechanism, due to the numerous interventions they undergo. When airway reflexes fail, commonly in the presence of dysphagia, aspiration can occur, which is the entry of a fluid or solid below the level of the true vocal cords. If left unmanaged, dysphagia has been associated with aspiration pneumonia, pneumonitis, airway obstruction, delayed enteral nutrition, prolonged length of ICU and hospital stay, reduced quality of life, and even death; in some cases, dysphagia is an independent risk factor for mortality. It is important to routinely assess dysphagia in all critically ill patients using a multimodal approach, including systematic assessments, scoring indices, trained specialists, and intensive care unit nurses. Several interventions are crucial for preventing and managing dysphagia and its associated problems. Further research is necessary to help determine the best ways to prevent and manage pulmonary aspiration in critically ill patients. Several interventions are essential in preventing and managing dysphagia and the sequelae of swallowing dysfunction. Further research is needed to help elucidate the best way to avoid and manage pulmonary aspiration in critically ill patients.
Bronchoscopic Lung Volume Reduction: A Review
Podder S, Khan M, Sink Z, Verga S, Kurman JS and Malsin E
Bronchoscopic lung volume reduction (BLVR) is an established treatment modality for the management of advanced chronic obstructive pulmonary disease complicated by severe emphysema and hyperinflation refractory to other therapies. BLVR aims to reduce hyperinflation and residual volume, thereby improving pulmonary function, symptom control, and quality of life. Multiple distinct devices and technologies, including endobronchial coils, thermal vapor ablation, bio-lung volume reduction, and airway bypass stenting, have been developed to achieve lung volume reduction with varying degrees of accessibility and evidence. The most promising BLVR treatment modality to date has been the placement of one-way endobronchial valves (EBVs), with more than 25,000 cases performed worldwide. Identifying symptomatic patients who would benefit from BLVR is challenging and can be time and resource intensive, and candidacy may be limited by physiologic parameters. Additional new technologies may be able to improve the identification and evaluation of candidates as well as increase the portion of evaluated patients who ultimately qualify for BLVR. In this review, we aim to provide historical context to BLVR, summarize the available evidence regarding its use, discuss potential complications, and provide readers with a clear guide to patient selection and referral for BLVR, with a focus on EBV placement. In addition, we will highlight potential future directions for the field.
Lung Transplant for Chronic Obstructive Pulmonary Disease
Swartz K, Mansour A and Alsunaid S
Chronic obstructive pulmonary disease (COPD) carries a high burden of morbidity and mortality to patient and a high cost to health care systems. Lung transplantation is a last resort available for end-stage COPD patients interested in pursuing it and meeting the strict transplant requirements. It requires commitment from patients and their loved ones to support them through this tough process. This review will cover history of transplant, indications, candidate selection, evaluation testing, transplant listing, type of transplant (single versus bilateral), posttransplant complications, immunosuppression, and rejection. It is tailored to the COPD patient when applicable; however, many aspects of lung transplantation are shared amongst all lung diseases eligible for transplant.
Informative Subtyping of Patients with Sepsis
Cafferkey J and Shankar-Hari M
Sepsis pathobiology is complex. Heterogeneity refers to the clinical and biological variation within sepsis cohorts. Sepsis subtypes refer to subpopulations within sepsis cohorts derived based on these observable variations and latent features. The overarching goal of such endeavors is to enable precision immunomodulation. However, we are yet to identify immune endotypes of sepsis to achieve this goal. The sepsis subtyping field is just starting to take shape. The current subtypes in the literature do not have a core set of shared features between studies. Thus, in this narrative review, we reason that there is a need to state the purpose of sepsis subtyping and minimum set of features that would be required to achieve the goal of precision immunomodulation for future sepsis.
How to Survive Sepsis: Patient Testimonial
Bracke K
Leaving university I started working for the Belgian National Radio as a journalist. I used to travel a lot and produce radio features about life abroad and how people all over the world dealt with the different challenges in society. A privileged job that I enjoyed doing for many years. In the meantime, I got married and became a mother of two sons. Nothing to worry about, so it seemed, until January 30, 2009. I had been fighting the symptoms of flu for some days. Instead of recovering, I began to feel worse and worse: I had a high fever, was asleep most of the time, could barely eat or drink, and had to cough a lot. The general practitioner sent me to hospital. A few hours later, I had to be reanimated. It was a close call: I was infected by the bacteria. My blood started thickening, my organs stopped functioning, and I went into a septic shock, followed by a cardiac arrest. I was successfully reanimated, but still not stable. For 10 days, I was fighting to survive at the intensive care unit (ICU), with several cardiac arrests and reanimations, some of which were long-lasting. The Head of the ICU informed my husband that there was less than 5% chance to survive and if so, he could not predict what kind of damage there would be: the amount of drugs that I had been given, including noradrenaline, was so extremely high, that it became very unclear how my body would respond to it. And if, as by miracle, I would survive: what kind of damage would there be? Physical? Mental? Physical and mental? No specialist could answer those questions. But both the health care professionals and my family fought to keep me alive.
Sepsis from Science to Social Perspective
Annane D and Ferrer R
Epigenetic Mechanisms in Sepsis-Associated Acute Kidney Injury
Fiorentino M, Philippe R, Palumbo CA, Prenna S, Cantaluppi V and Rosa S
Sepsis, the dysregulated immune response of the host to infections, leads to numerous complications, including multiple organ dysfunction with sepsis-associated acute kidney injury (SA-AKI) being a frequent complication associated with increased risk of mortality and the progression toward chronic kidney disease (CKD). Several mechanisms have been widely investigated in understanding the complex pathophysiology of SA-AKI, including hemodynamic alterations, inflammation, oxidative stress, and direct cellular injury driven by pathogens or cell-derived products (pathogen-associated molecular patterns and damage-associated molecular patterns). Despite advancements in the management of septic patients, the prognosis of SA-AKI patients remains significantly poor and is associated with high in-hospital mortality and adverse long-term outcomes. Therefore, recent research has focused on the early identification of specific SA-AKI endotypes and subphenotypes through epigenetic analysis and the use of potential biomarkers, either alone or in combination with clinical data, to improve prognosis. Epigenetic regulation, such as DNA methylation, histone modifications, and noncoding RNA modulation, is crucial in modulating gene expression in response to stress and renal injury in SA-AKI. At the same time, these modifications are dynamic and reversible processes that can alter gene expression in several pathways implicated in the context of SA-AKI, including inflammation, immune response, and tolerance status. In addition, specific epigenetic modifications may exacerbate renal damage by causing persistent inflammation or cellular metabolic reprogramming, leading to progression toward CKD. This review aims to provide a comprehensive understanding of the epigenetic characteristics that define SA-AKI, also exploring targeted therapies that can improve patient outcomes and limit the chronic progression of this syndrome.
Management of Sepsis in the First 24 Hours: Bundles of Care and Individualized Approach
Coloretti I, Tosi M, Biagioni E, Busani S and Girardis M
Early diagnosis and prompt management are essential to enhance the outcomes of patients with sepsis and septic shock. Over the past two decades, evidence-based guidelines have guided appropriate treatment and recommended the implementation of a bundle strategy to deliver fundamental treatments within the initial hours of care. Shortly after its introduction, the implementation of a bundle strategy has led to a substantial decrease in mortality rates across various health care settings. The primary advantage of these bundles is their universality, making them applicable to all patients with sepsis. However, this same quality also represents their primary disadvantage as it fails to account for the significant heterogeneity within the septic patient population. Recently, the individualization of treatments included in the bundle has been suggested as a potential strategy for further improving the prognosis of patients with sepsis. New strategies for the early identification of microorganisms and their resistance patterns, advanced knowledge of antibiotic kinetics in critically ill patients, more conservative fluid therapy in specific patient populations, and early use of alternative vasopressors to catecholamines, as well as tailored source control based on patient conditions and site of infection, are potential approaches to personalize initial care for specific subgroups of patients. These innovative methodologies have the potential to improve the management of septic shock. However, their implementation in clinical practice should be guided by solid evidence. Therefore, it is imperative that future research evaluate the safety, efficacy, and cost-effectiveness of these strategies.
Five Questions to Help Prompt End-of-Life Planning in Neuromuscular Disease
Lipanot BJ and Bosslet G
Patients with neuromuscular disease are living longer lives but continue to have significant and often unpredictable morbidity and mortality. End-of-life planning for these patients is thus an essential part of their medical care. This planning should include the following topics: health care surrogates, swallowing and nutrition, daytime respiratory support, and all aspects of when end of life is near. and diseases may require different approaches to these topics. All patients with neuromuscular disease will benefit from these discussions to best reach patient-centered goals. We present health care providers these five questions and explanations as a guide.