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Laryngopharyngeal reflux (LPR), often called "silent reflux," is a challenging condition that affects the upper airway, causing persistent throat symptoms such as hoarseness, chronic cough, excess mucus, and a sensation of something stuck in the throat. Unlike typical acid reflux, which affects the oesophagus, LPR causes irritation higher up, around the voice box and throat, where tissues are especially sensitive. Proton pump inhibitors (PPIs) are commonly prescribed as a first-line treatment, but these medications often do not work for everyone, particularly when reflux affects the throat. This has led to growing interest in new treatment approaches that deliver medication more precisely to the affected area.
A new study published in the Journal of Aerosol Science has investigated whether dry powder inhalers (DPIs) – devices commonly used for asthma and other lung conditions – could be adapted to deliver drugs directly to the laryngopharynx【1】. This research could pave the way for a novel treatment strategy for LPR, offering hope to patients who do not respond to traditional therapies.
LPR and asthma frequently coexist in the same individual, and controlling LPR has been associated with improved asthma control【3】. However, effective treatment for LPR has long been elusive. PPIs, which reduce gastric acid secretion, often provide incomplete relief for LPR because the condition is driven not only by acid but also by the digestive enzyme pepsin, which can remain active even at neutral pH. Moreover, the anatomical location of LPR – deep in the throat – makes it difficult for oral medications to reach the affected tissues in sufficient concentrations.
This has led researchers to explore alternative delivery methods. Dry powder inhalers, which are routinely used to deliver asthma medications directly to the lungs, offer a potential solution: if these devices could be optimised to deposit medication in the laryngopharynx, they might provide targeted therapy for LPR with fewer systemic side effects.
The researchers, including Nikki Johnston from the Medical College of Wisconsin, used detailed computer simulations of the human airway to explore how medication particles travel during inhalation. Their goal was to identify the best way to deliver drugs to the laryngopharynx, the area of the throat often affected in LPR.
They tested three different particle sizes (3 μm, 10 μm, and 50 μm), variations in inhalation depth (shallow to forceful) and duration (short vs. long breaths), and the effect of exit velocity (how fast medication leaves the inhaler).
The standout result from the study was that particle size had the greatest impact on drug delivery to the throat. Particles measuring 10 micrometres (μm) delivered the highest dose to the laryngopharynx—around 20% of the emitted dose. In contrast, smaller (3 μm) and larger (50 μm) particles were much less effective, delivering only 2–5%【1】.
The researchers also found that breathing style had little influence, suggesting that inhaler design plays a bigger role than how a patient uses it. These findings highlight the importance of optimising inhaler particle size if the goal is to target reflux symptoms in the upper airway.
Although the study did not evaluate any specific medications, its findings are highly relevant for future treatment strategies, particularly those aimed at conditions like LPR, where targeting the throat directly is key. One area of particular interest is pepsin, a digestive enzyme that has been identified as a key driver of inflammation and tissue damage in LPR. The ability to deliver drugs directly to the laryngopharynx using a dry powder inhaler could open the door to pepsin-inhibiting therapies, anti-inflammatory agents, or mucosal protectants that act exactly where they are needed. This approach would minimise systemic exposure and potentially improve tolerability.
Recent clinical guidelines for the management of LPR recommend that empirical treatment be based on diet, stress reduction, and alginates or antacids to address both acidic and alkaline reflux events, while PPIs are reserved for patients with acidic LPR and GERD findings【2】. This underscores that a one-size-fits-all approach is insufficient – and that novel targeted delivery methods could fill an important gap.
As new therapies like targeted inhalers emerge, accurate diagnosis becomes even more critical. Pepsin testing – such as with the Pepfast saliva test – provides a non‑invasive, objective way to diagnose LPR by measuring pepsin, the stomach enzyme that should never appear in saliva. By confirming that reflux is indeed the cause of a patient's throat symptoms, pepsin testing can help guide treatment decisions and monitor response to therapy. For patients who do not respond to PPIs, a positive pepsin test may indicate that alternative approaches – such as DPI-delivered therapies – are warranted.
The repurposing of asthma inhalers for LPR treatment represents an innovative concept that could transform the management of this common but often difficult-to-treat condition. By optimising particle size to target the laryngopharynx, dry powder inhalers could deliver medications precisely where they are needed, offering new hope for patients who have failed standard therapy. As this research advances, objective diagnostic tools such as pepsin testing will play an essential role in identifying appropriate candidates and monitoring treatment outcomes.
Q1: Can asthma inhalers currently be used to treat LPR?
A1: Not yet. The research is still at the computational modelling stage. However, the study demonstrates that dry powder inhalers could be optimised to deliver medication to the laryngopharynx, which may lead to future LPR treatments【1】.
Q2: Why don't standard acid reflux medications work well for LPR?
A2: LPR is caused not only by acid but also by pepsin, a digestive enzyme that remains active even at neutral pH. PPIs reduce acid but do not affect pepsin; they also may not reach the throat in sufficient concentrations.
Q3: How does pepsin testing help with LPR management?
A3: Pepsin testing detects the presence of the stomach enzyme in saliva – direct evidence that reflux has occurred. This objective confirmation can guide treatment decisions and help identify patients who might benefit from novel therapies.
Q4: What particle size is optimal for targeting the throat with an inhaler?
A4: The study found that 10 μm particles delivered the highest dose to the laryngopharynx (around 20% of the emitted dose), whereas smaller or larger particles were significantly less effective【1】.
Q5: What types of medications could be delivered via this method?
A5: Potential candidates include pepsin inhibitors, anti-inflammatory agents, alginates (which form a protective barrier), and mucosal protectants – all delivered directly to the affected throat tissues.
【1】Johnston N, Chen A, Smith J, et al. Dry powder inhalers for targeted drug delivery to the laryngopharynx: a computational study. Journal of Aerosol Science. 2025;185:106389.
【2】Lechien JR, Chiesa-Estomba CM, Hans S, et al. European clinical practice guideline for managing and treating laryngopharyngeal reflux disease. European Archives of Oto-Rhino-Laryngology. 2025;282(4):1459-1478.
【3】Kiljander TO, Salomaa ER, Hietanen EK, Terho EO. Treatment of laryngopharyngeal reflux improves asthma symptoms in asthmatics. Journal of Asthma. 2016;53(7):709-715.
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