The global increase in obesity, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD) has led to a higher use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among patients undergoing gastrointestinal endoscopy. Although GLP-1RAs provide significant metabolic, cardiovascular, and hepatic benefits, their tendency to slow gastric emptying has raised concerns about retained gastric contents (RGC), procedural complications, and a greater risk of pulmonary aspiration during sedation or anesthesia. This review offers a translational narrative synthesis of mechanistic, physiological, and clinical evidence connecting GLP-1RA therapy to changes in gastric motility and peri-endoscopic outcomes. Data from pharmacological studies, scintigraphic evaluations, large observational cohorts, and international consensus statements are combined to guide physiology-based procedural decisions. Evidence consistently indicates that GLP-1RA exposure is associated with a higher incidence of RGC and more frequent procedural disruptions during upper gastrointestinal endoscopy. However, it remains uncertain whether RGC leads to clinically significant aspiration. Consistent with this, real-world data reveal no increase in aspiration pneumonia among GLP-1RA users undergoing colonoscopy, with reported aspiration rates of approximately 0.01%-0.05%. Likewise, during upper gastrointestinal endoscopy, only a small absolute rise in aspiration-related events has been observed, involving fewer than 0.3% of procedures. Current guidelines favor continuing GLP-1RA therapy alongside dietary modification, structured risk assessment, selective gastric point-of-care ultrasound (POCUS), and multidisciplinary communication, rather than routine cessation. Emerging prospective evidence indicates that implementing a pre-procedural clear liquid diet, with individualized timing of weekly agents, may reduce the risk of clinically significant RGC, complementing existing dietary preparation strategies.

Aspiration-related lung diseases comprise a broad spectrum of disorders resulting from the entry of oropharyngeal or gastric contents into the lower respiratory tract. Clinical manifestations range from acute aspiration pneumonitis and aspiration pneumonia to chronic airway and parenchymal injury, including bronchiolitis, bronchiectasis, fibrosis, and lipoid pneumonia. Aspiration pneumonitis is driven primarily by chemical injury, whereas aspiration pneumonia results from infection caused by aspirated microorganisms in susceptible hosts. Contemporary microbiologic data indicate that aspiration pneumonia more closely resembles community- or hospital-acquired pneumonia than the classic anaerobic infection paradigm. Imaging plays a central role in diagnosis, yet radiographic findings are highly variable and frequently contribute to diagnostic uncertainty. Chest radiography may be entirely normal or demonstrate only subtle gravity-dependent or perihilar opacities, while in other cases it reveals multifocal or diffuse air-space opacities that overlap substantially with other infectious and inflammatory lung diseases. Computed tomography is considerably more sensitive and depicts a broad spectrum of acute and chronic aspiration-related abnormalities, including ground-glass opacities, consolidation, tree-in-bud opacities, centrilobular nodules, aspiration bronchiolitis, bronchiectasis, fibrotic remodeling, and dendriform pulmonary ossification, while also demonstrating characteristic findings in select aspiration-related conditions. Recognition of these imaging patterns, together with clinical history and swallowing evaluation, is critical for establishing the diagnosis and identifying the underlying mechanism of aspiration. Management requires integration of clinical history, imaging, swallowing assessment, and selective adjunctive testing, with treatment directed toward supportive care, appropriate antimicrobial therapy when infection is present, prevention of recurrent aspiration through correction of the underlying cause, and multidisciplinary management when indicated. Early diagnosis and intervention are essential to prevent recurrent lung injury and progressive pulmonary damage.

Aspiration is the unintentional passage of material from the oropharynx or gastrointestinal tract into the larynx, tracheobronchial tree, or lung parenchyma. Aspirated material may include saliva, oral secretions, food, liquids, gastric contents, bile, blood, or foreign material. Although small-volume aspiration may occur without clinically apparent disease, aspiration can cause airway obstruction, chemical pneumonitis, bacterial pneumonia, acute hypoxemic respiratory failure, acute respiratory distress syndrome, lung abscess, empyema, bronchiectasis, or chronic aspiration-related lung disease. Normal swallowing requires coordinated oral, pharyngeal, and esophageal phases. During the pharyngeal phase, elevation of the larynx, epiglottic inversion, vocal-fold closure, pharyngeal contraction, and an effective cough reflex help prevent material from entering the lower respiratory tract. Dysfunction at any stage may impair airway protection. Aspiration risk is therefore increased in patients with oropharyngeal dysphagia, neurologic disease, impaired consciousness, sedative exposure, neuromuscular weakness, structural head and neck disease, esophageal dysmotility, gastroesophageal reflux, vomiting, or delayed gastric emptying. Aspiration syndromes are classified according to aspirate composition, volume, bacterial burden, site of deposition, and temporal pattern. Macroaspiration refers to the inhalation of a clinically significant volume of material and may cause abrupt airway obstruction or acute lung injury. Microaspiration is often recurrent and clinically silent but may contribute to aspiration pneumonia or chronic airway injury in susceptible patients. Aspiration pneumonitis is an acute inflammatory lung injury caused by inhalation of noxious material, most often acidic gastric contents. In contrast, aspiration pneumonia is an infectious process that follows aspiration of colonized oropharyngeal secretions or gastrointestinal contents into the lower respiratory tract. These syndromes may overlap, particularly when partially digested gastric contents contain both acidic material and bacteria. The clinical course ranges from asymptomatic aspiration to rapidly progressive respiratory compromise. Chemical pneumonitis typically develops soon after a witnessed macroaspiration event, whereas aspiration pneumonia may develop more insidiously after unwitnessed or recurrent aspiration. Older adults and patients with frailty, stroke, dementia, Parkinson disease, critical illness, or impaired swallowing are disproportionately affected and may have recurrent events with substantial morbidity and mortality. Aspiration-related lung injury generally follows gravity-dependent bronchopulmonary segments. In patients who aspirate while upright, infiltrates commonly involve the basal lower-lobe segments. In recumbent patients, the posterior upper lobes and superior segments of the lower lobes are more often affected. The right lung is frequently involved because of the more vertical course of the right main bronchus, although bilateral or nondependent disease may occur depending on body position, aspirate volume, and underlying lung disease. Recognition of aspiration risk and early differentiation among airway obstruction, aspiration pneumonitis, and aspiration pneumonia are essential, as diagnostic evaluation, airway management, antimicrobial therapy, and preventive interventions should be individualized to the clinical setting and suspected aspirate.

Bronchiectasis is a heterogeneous chronic lung disease marked by irreversible airway dilation and damage, instigating symptoms of chronic cough, dyspnea, and excessive mucus production. Recurrent exacerbations or infections with ongoing inflammation can lead to impaired quality of life, reduced ability to clear mucus, and even respiratory failure. Dozens of distinct conditions can contribute or coexist with bronchiectasis, often fueling a self-perpetuating vortex of inflammation, infection, and airway remodeling. Aspiration resulting in foreign particles into the airway can cause chemical pneumonitis from gastric contents, airway inflammation, and/or infection, with repeated exposures producing chronic injury. As clinical expertise has grown, aspiration-related pathology has acquired attention as a potential contributor to bronchiectasis and chronic lung infections, including nontuberculous mycobacteria, extrapolating from characterized relationships in other chronic lung diseases. Nonspecific symptoms, diagnostic challenges, and incomplete data characterizing the relationship have hindered the development of clear guidelines. In addition, the necessity for multidisciplinary care can delay timely management. Here, we assembled a multidisciplinary team of experts to evaluate retrograde and anterograde aspiration as modifiable comorbidities to bronchiectasis through case-based formatting. Using this framework and a narrative literature review, this How I Do It article provides clinical perspective on who, when, and how to test for aspiration from swallowing dysfunction and reflux disease. The study purpose was to raise awareness of aspiration, enhance evaluation by improving the pulmonologist's knowledge of test selection and interpretation, highlight the value of cross-disciplinary discussion, outline basic management strategies, and inspire further studies within bronchiectasis and chronic lung infection populations.

Gastroesophageal reflux-related cough (GERC) is a common etiology of chronic cough, characterized by a complex pathogenesis. The limited efficacy of conventional acid suppression therapy suggests the presence of critical mechanisms that extend beyond mere gastric acid irritation. This review systematically explores the interaction between the two core pathways-"microaspiration" and "neurogenic inflammation"-in the context of GERC, aiming to elucidate their synergistic pathogenic mechanisms. On one hand, the gastric contents involved in microaspiration (such as gastric acid and pepsin) directly damage the airway mucosal barrier, activating local chemical inflammatory responses and specific receptors like transient receptor potential vanilloid subfamily member 1 (TRPV1). On the other hand, esophageal reflux can trigger a reflex arc mediated by the vagus nerve, prompting airway sensory nerves to release neuropeptides such as substance P, thereby initiating neurogenic inflammation and ultimately leading to heightened cough hypersensitivity. These two pathways do not exist in isolation; rather, they constitute a critical "injury-sensitization-reinjury" positive feedback loop: inflammation induced by micro-aspiration can sensitize sensory nerves, exacerbating neural reflexes; conversely, the severe cough resulting from neurogenic inflammation elevates intra-abdominal pressure, further promoting reflux and aspiration. A deep understanding of this interactive mechanism not only provides a comprehensive mechanistic basis for explaining refractory GERC but also lays the theoretical groundwork for developing novel combined therapeutic strategies that target both mucosal protection and neural modulation.

Cough is a powerful, protective expulsive behavior that assists in maintaining respiratory health by clearing foreign material, pathogens, and mucus from the airways. Therefore, cough is critical to survival in both health and disease. Importantly, cough protects the airways and lungs from both antegrade (e.g., food, liquid, saliva) and retrograde (e.g., bile, gastric acid) aspirate contents. Aspiration is often the result of impaired swallowing (dysphagia), which allows oral and/or gastric contents to enter the lung, especially in individuals who also have cough dysfunction (dystussia). Cough hyposensitivity, downregulation, or desensitization- collectively referred to as hypotussia- is common in individuals with dysphagia, and increases the likelihood that aspirated material will reach the lung. The consequence of hypotussia with reduced airway clearance can include respiratory tract infection, chronic inflammation, and long-term damage to the lung parenchyma. Despite the clear implications for health, the problem of managing hypotussia in individuals with dysphagia is frequently overlooked. Here, we provide an overview of the current interventions and treatment approaches for hypotussic cough. We synthesize the available literature to summarize research findings that advance our understanding of these interventions, as well as current gaps in knowledge. Further, we highlight pragmatic resources to increase awareness of hypotussic cough interventions and provide support for the clinical implementation of evidence-based treatments. In culmination, we discuss potential innovations and future directions for hypotussic cough research.

Glucagon-like peptide-1 receptor agonists are an emerging class of medications transforming the management of diabetes mellitus and obesity, two highly prevalent and chronic medical conditions associated with significant morbidity and posing serious public health concerns. Although generally well tolerated and relatively safe to use, case reports of patients taking these medications while undergoing elective procedures with general anesthesia describe a potential heightened risk of regurgitation and pulmonary aspiration of gastric contents, deriving from the delayed gastric emptying effect of these agents. Based on increased recognition of this risk, the American Society of Anesthesiologists convened a task force to review available data, resulting in the promulgation of a new procedural management guideline for patients on these drugs and undergoing elective procedures with general anesthesia. However, this guideline pertains mostly to procedures and situations that are distinct from electroconvulsive therapy (ECT). This case report describes the experience of a patient on semaglutide, a glucagon-like peptide-1 receptor agonist for obesity, undergoing ECT, provides a general overview of this novel drug class, identifies issues specific to ECT management, and suggests potential adaptations to patient care over different phases of ECT practice.