Semaglutide‐Induced Silent Aspiration: An Unrecognised Cause of Organising Pneumonia

ABSTRACT

We present the case of a female in her 20s with a history of obesity and obstructive sleep apnea (OSA) on continuous positive airway pressure (CPAP) therapy, who developed silent microaspiration pneumonitis and organising pneumonia (OP) following the recent initiation of Semaglutide for weight loss. She initially presented with shortness of breath, a non‐productive cough and subjective fevers of 1‐week duration. On admission, she was hypoxic, requiring 6 L of oxygen via nasal cannula and chest imaging revealed right lung infiltrates concerning for community‐acquired pneumonia. Despite completing antibiotics, her symptoms and imaging progressively worsened. An extensive infectious and autoimmune workup was conducted, but no clear aetiology was identified. Diagnostic bronchoscopy revealed severe gastroesophageal reflux disease (GERD) with evidence of microaspiration, leading to the diagnosis of organising pneumonia (OP) secondary to silent aspiration. Although long‐acting glucagon‐like peptide‐1 (GLP‐1) agonists like Semaglutide do not typically cause reflux, they are known to delay gastric emptying, which can increase intragastric pressure. In this patient, the combination of delayed gastric emptying from Semaglutide, obesity and CPAP therapy likely contributed to reflux and silent aspiration. The patient was successfully treated with corticosteroids and proton pump inhibitors, resulting in clinical and radiographic improvement. This case highlights the potential for silent aspiration in patients on GLP‐1 receptor agonists, especially those on CPAP therapy, and underscores the importance of monitoring for reflux‐related complications in these patients.

Semaglutide, a GLP‐1 receptor agonist, may contribute to silent aspiration in high‐risk patients by delaying gastric emptying. This case highlights organising pneumonia secondary to microaspiration in a patient on CPAP therapy and Semaglutide, with marked radiographic improvement following corticosteroids.

1. Introduction

Semaglutide is a GLP‐1 receptor agonist (GLP‐1RA) indicated for Type 2 diabetes and chronic weight management [1]. By mimicking incretin hormones, it enhances glucose‐dependent insulin secretion while suppressing glucagon, and it slows gastric emptying [1]. Interestingly, gastric stasis from Semaglutide has raised concerns about gastroesophageal reflux and potential aspiration of gastric contents [2, 3].

Recent case reports and clinical observations have documented aspiration events in Semaglutide‐treated patients, even after extended fasting periods, prompting anaesthesia societies and the FDA to issue precautions about aspiration under sedation [4, 5]. Notably, the American Society of Anesthesiologists now recommends holding weekly dosed GLP‐1 agonists for at least. One week before elective procedures [5]. Chronic or ‘silent’ aspiration is an underrecognized cause of interstitial lung injury [6]. Delayed gastric emptying and refractory GERD can lead to occult microaspiration of acidic contents, particularly in patients with OSA during sleep, without obvious choking episodes [6]. Repeated microaspiration events can instigate chemical pneumonitis and subacute inflammation in the lungs [6]. Aspiration pneumonitis is a well‐described trigger for organising pneumonia (OP)—an inflammatory pulmonary process wherein the injured lung tissue heals with organised fibrosis rather than resolution [4]. OP, whether cryptogenic or secondary to aspiration, typically shows bilateral, subpleural or peribronchial opacities [7]. Radiographic hallmarks such as peripheral consolidation, the reversed halo sign and bandlike subpleural infiltrates may aid in distinguishing OP from other pulmonary pathologies [7].

The diagnosis of OP hinges on excluding infection and demonstrating the characteristic organising fibroblastic tissue on lung biopsy, unless a classic clinical‐radiographic presentation with a known precipitant allows a presumptive diagnosis [8]. Importantly, OP is not an infection; it often responds dramatically to corticosteroids, with most patients recovering fully over weeks to months [4].

2. Case Report

A female in her 20s with a history of morbid obesity (BMI 42 kg/m²) and OSA (on nightly CPAP) presented with a 1‐week history of shortness of breath, non‐productive cough and subjective fevers. Two days prior, she had visited the emergency department (ED) for similar symptoms, where imaging showed right upper lobe consolidation and she was discharged on oral amoxicillin for community‐acquired pneumonia (Figure 1). At home, her symptoms worsened, and home pulse oximetry showed 85% oxygen saturation on room air, prompting her return to the ED. Her only significant history was the recent initiation of Semaglutide for weight loss 3 weeks prior. She had no prior diagnosis of GERD and had not reported reflux symptoms before Semaglutide. However, after starting the medication, she noted increased postprandial bloating and intermittent regurgitation, which she had initially dismissed.

FIGURE 1.

Initial antero‐posterior (AP) chest x‐ray (CXR) and chest CT on first presentation to the ED, showing findings that led to discharge with oral amoxicillin for presumed community‐acquired pneumonia.

In the ED, the patient was tachycardic (heart rate in the 110 s), tachypnoeic (respiratory rate in the 20 s) and hypoxic, requiring 6 L of oxygen via nasal cannula. Labs revealed a normal WBC count (5.7) and mild anaemia (Hgb 9.6). CMP and arterial blood gases (ABGs) were unremarkable. COVID‐19 and influenza tests were negative. Repeat CXR showed worsening bilateral infiltrates (Figure 2A), and chest CT demonstrated severe bilateral patchy airspace disease with worsening right lung consolidation (Figure 2B).

FIGURE 2.

(A) Anteroposterior chest radiograph on hospital readmission (Day 2) shows bilateral worsening infiltrates, particularly, in the right mid and lower lung zones, with new involvement of the left base.(B–C) High‐resolution axial chest CT images from the same day reveal bilateral patchy airspace disease and evolving consolidation, more prominent in the dependent posterior segments of the right lung. These findings are suggestive of subacute pneumonitis and raised suspicion for silent aspiration in the absence of infectious response. (D) Chest radiograph on Day 6 shows persistent and worsening bilateral infiltrates despite completion of broad‐spectrum antibiotics, prompting bronchoscopy. (E) By Day 9, after initiation of corticosteroid therapy, the CXR demonstrates marked radiographic improvement, consistent with organising pneumonia. (F) On Day 11 (discharge), the final chest radiograph reveals near‐complete resolution of infiltrates. The patient's oxygen requirement had resolved, and she was discharged on a steroid taper and proton pump inhibitor.

The patient was admitted to the hospital and started on IV Ampicillin‐Sulbactam and IV Doxycycline for suspected CAP. Blood cultures, sputum cultures and antigen testing for Streptococcus pneumoniae and Legionella were sent.

Two days after admission, her oxygen requirements worsened to 10 L via NC, with radiographic evidence of worsening bilateral lung infiltrates. Pulmonary and infectious disease consults were obtained. Given her family history of granulomatosis with polyangiitis, a broad infectious, autoimmune, and vasculitis workup was ordered, including ANCA panels, mycoplasma antibodies, respiratory viral panel and fungal studies. All results were negative, reducing suspicion for infectious aetiology. Despite completing antibiotics, the patient showed no clinical improvement. Silent aspiration secondary to recent Semaglutide initiation was considered. Bronchoscopy on Day 6 revealed diffuse erythema and mucosal changes in the posterior trachea suggestive of reflux injury. While small white plaques were noted, bronchoalveolar lavage cultures and cytology were negative for fungal or malignant processes, supporting a non‐infectious aetiology. Imaging continued to show persistent or worsening infiltrates (Figure 2D). Transbronchial biopsy was not performed.

Given the bronchoscopy findings, a diagnosis of OP secondary to microaspiration pneumonitis was made. The patient was started on oral prednisone 40 mg daily and pantoprazole 40 mg daily for GERD. Semaglutide was discontinued indefinitely.

The patient's oxygen requirements progressively improved, and repeat imaging showed resolution of the infiltrates. Imaging 2 days after initiating steroids showed marked radiographic improvement (Figure 2E), and she was weaned off oxygen by Day 10. She was discharged home on room air on Day 11 with a tapering dose of prednisone and ongoing PPI therapy. Final imaging at discharge showed near‐complete resolution of prior infiltrates (Figure 2F). A summary of the patient's clinical course and imaging progression is presented in Table 1.

TABLE 1.

Hospital course timeline with key interventions and imaging findings.

Day	Clinical events and imaging
ED visit (Day 0)	Initial presentation with SOB, cough, subjective fevers. CXR and CT showed right upper lobe consolidation → diagnosed with CAP, discharged on amoxicillin (Figure 1).
Readmission (Day 2)	Returned with worsening hypoxia. Repeat CXR showed bilateral infiltrates. (Figure 2A) CT revealed progressive bilateral consolidation (Figure 2B,C).
Day 3	Worsening oxygen needs; extensive infectious and autoimmune workup initiated.
Day 6	Completed antibiotics without improvement. Bronchoscopy showed GERD with microaspiration. CXR showed worsening infiltrates (Figure 2D).
Day 7	Initiation of prednisone and pantoprazole.
Day 9	Notable clinical and radiologic improvement post‐steroids (Figure 2E).
Day 11 (discharge)	Off oxygen, CXR demonstrated resolution of infiltrates (Figure 2F).

3. Discussion

Our case illustrates a rare clinical scenario in which OP developed following chronic, silent microaspiration in a patient with OSA on CPAP and taking Semaglutide. To our knowledge, this is among the first published reports of such a case. The patient's risk factors of obesity with GERD and OSA on CPAP likely compounded the effects of Semaglutide‐induced gastroparesis. While the patient had predisposing factors for aspiration, she had no documented aspiration episodes or abnormal chest imaging prior to starting Semaglutide. The emergence of progressive pulmonary infiltrates, unexplained respiratory symptoms and bronchoscopy‐confirmed reflux injury shortly after Semaglutide initiation points towards a temporal relationship and possible drug‐induced mechanism.

GLP‐1 agonists like Semaglutide seldom cause frank aspiration in the absence of other factors; indeed, large cohort studies have found at most a slight increase in aspiration pneumonitis events among GLP‐1RA users undergoing endoscopy, without a rise in severe outcomes [9]. However, in this patient, the combination of delayed gastric emptying, CPAP‐related aerophagia and nocturnal reflux created a perfect milieu for silent aspiration. Clinicians should remain vigilant for non‐infectious pulmonary complications in patients on GLP‐1 agonists who have comorbid conditions (such as OSA) that predispose to aspiration.

Semaglutide's pharmacologic effects on gastric motility provide a plausible mechanism for the observed aspiration. GLP‐1 receptor activation in the gut and vagal pathways slows peristalsis and gastric emptying. This can increase intragastric volume and pressure, promoting gastroesophageal reflux in susceptible individuals [3, 4, 9]. CPAP therapy for OSA is another key contributor to this patient's course. CPAP delivers positive airway pressure to stent the upper airway open, but it can inadvertently force air into the oesophagus and stomach (a phenomenon known as aerophagia) [10]. Aerophagia has been associated with an increased incidence of GERD symptoms in CPAP users [10]. The elevated intrathoracic and intra‐abdominal pressures during CPAP can transiently overcome the lower oesophageal sphincter, leading to reflux of gastric contents [10]. In the case of our patient, it is plausible that nighttime CPAP use facilitated the regurgitation and microaspiration of semi‐digested gastric contents.

Silent aspiration refers to the inhalation of small amounts of refluxate without cough or choking and is a known risk in OSA patients—especially when GERD is uncontrolled [6]. Over time, repeated silent aspirations can cause chronic chemical pneumonitis and, in severe cases, lead to OP or other interstitial lung disease [6]. The unique interplay of Semaglutide and CPAP in our patient—one factor increasing gastric contents and the other promoting their aspiration—ultimately resulted in an inflammatory lung injury.

Despite initial treatment for presumed community‐acquired pneumonia, the patient's condition evolved into non‐resolving pneumonitis. Diagnostic bronchoscopy was pivotal: it revealed signs of severe reflux injury in the airway, including diffuse tracheal erythema—a finding that has been correlated with gastroesophageal reflux disease in prior studies [11]. Bronchoalveolar lavage and cytology were also performed to exclude infectious or malignant etiologies, with negative results. Transbronchial biopsy was not performed, but these features, combined with the clinical context of GERD and aspiration, solidified the diagnosis.

Oral corticosteroids are the first‐line therapy for OP, typically inducing improvement within 1–2 weeks and radiologic clearing over 1–3 months [8]. Relapses are not uncommon, especially if the underlying insult persists; thus, a slow steroid taper and close monitoring are recommended. In this case, removal of the precipitating factors was paramount: Semaglutide was held indefinitely, and the patient's CPAP settings were adjusted in concert with weight loss and GERD management. This case highlights how pharmacologic agents like GLP‐1 receptor agonists (that are often assumed to be benign), can carry unexpected risks in the presence of overlapping vulnerabilities, such as OSA and CPAP use.

In conclusion, this case illustrates a rare but significant complication of Semaglutide use in a patient with OSA on CPAP therapy, where the interplay of medication‐induced GERD and continuous positive airway pressure led to silent aspiration and OP. This unusual presentation highlights the importance of considering GLP‐1 receptor agonists as a potential risk factor for microaspiration in patients with predisposing conditions like OSA. Clinicians should maintain a high index of suspicion for non‐infectious pulmonary complications in patients on GLP‐1 agonists who develop unexplained respiratory symptoms. Prompt recognition and management of microaspiration through proton pump inhibitors and corticosteroids can result in positive outcomes, as shown in this case.

Author Contributions

K.E.‐Q. contributed to conceptualisation of the manuscript, manuscript original drafting and served as a clinical supervisor. G.M. was responsible for manuscript editing, figure organisation and submission. H.H. assisted with the development of the case presentation and contributed to manuscript revisions. M.K. contributed to the writing and revisions of the manuscript. P.O. and M.J. served as senior authors, providing expert review and oversight.

Consent

The authors declare that written informed consent was obtained for the publication of this manuscript and accompanying images and attest that the form used to obtain consent from the patient complies with the Journal requirements as outlined in the author guidelines.

Conflicts of Interest

The authors declare no conflicts of interest.

Essilfie‐Quaye K., Maule G., Hashim H., Khraisat M., Okonoboh P., and Jantz M., “Semaglutide‐Induced Silent Aspiration: An Unrecognised Cause of Organising Pneumonia,” Respirology Case Reports 13, no. 7 (2025): e70249, 10.1002/rcr2.70249.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.