Factors associated with olfactory recovery under biologic therapy in chronic rhinosinusitis with nasal polyps: the BIOPOSE prospective multicentre cohort

For millions of people, the world has lost a layer of texture and memory. Chronic rhinosinusitis with nasal polyps is a persistent inflammatory condition where soft, non-cancerous growths develop inside the nose and sinuses. These growths are driven by a specific type of immune system overreaction, often linked to asthma, that causes swelling and blockage. While the physical congestion is difficult, the loss of smell is often the most devastating consequence. Without the ability to smell, food loses its flavor, danger signals like smoke or gas go undetected, and the emotional connection to scents—like rain on pavement or a loved one's perfume—vanishes. For years, the standard treatment involved surgery to remove the polyps and steroid sprays to reduce swelling, but for many, the smell never fully returned, or it faded again quickly.

In recent years, a new class of medicines known as biologics has offered hope. These are laboratory-made proteins designed to target and block the specific chemical signals that drive the inflammation in the nose. Two such drugs, one that blocks a receptor for two key inflammatory chemicals and another that targets a single chemical called interleukin-5, have shown great promise in shrinking polyps and helping patients breathe. However, doctors and patients alike have noticed a frustrating gap: while these drugs work well for many, a significant number of people still cannot smell after taking them. The question became whether there was a way to predict who would regain their sense of smell and who would not, allowing for better expectations and choices before starting these expensive treatments.

Researchers in France set out to answer this question by following a large group of patients over the course of a year. They gathered data from fifteen different hospitals, tracking adults with severe, uncontrolled nasal polyps who had just started treatment with one of these two biologic drugs. The team focused specifically on the patients' sense of smell, asking them to rate their ability to detect odors on a scale from zero to one hundred at the start of the study and again after twelve months. They defined "recovery" as either a score indicating a very good sense of smell or a massive improvement of at least fifty points from where they started. The study included 427 patients in total, but the final analysis focused on the 116 individuals who had complete records for both the beginning and the end of the year, ensuring the data was solid enough to draw conclusions.

The results revealed a clear pattern in who recovered their sense of smell. Out of the 116 patients analyzed, about sixty percent managed to regain a functional sense of smell by the twelve-month mark. When the researchers looked closely at the history of these patients, two specific factors stood out as strong predictors of success. The first was a simple, low-tech test: had the patient's sense of smell improved when they took a short course of oral steroid pills in the past? Among those who recovered their smell on the biologic drugs, nearly two-thirds had previously shown a positive response to these steroid pills. In contrast, only a tiny fraction of those who did not recover had ever responded to steroids in the past. This suggests that if the olfactory nerves are still capable of waking up when given a strong anti-inflammatory boost, they are likely to respond well to the newer biologic treatments as well.

The second factor was the specific type of drug the patient received. The study found that patients who started on the drug that blocks the receptor for two inflammatory chemicals were significantly more likely to recover their smell compared to those who started on the drug targeting only the single chemical. While the study was not a randomized trial where patients were assigned drugs by chance, the difference was striking enough to suggest that the broader drug might be more effective for this specific symptom. The researchers noted that this finding aligns with the idea that smell recovery depends on clearing a specific type of inflammation in the narrow passages of the nose, rather than just shrinking the visible polyps. Interestingly, other common factors that doctors often worry about, such as how many times a patient had undergone sinus surgery in the past, how long they had suffered from the disease, or their blood levels of a specific white blood cell called eosinophils, did not predict whether the smell would return.

Despite these clear findings, the authors are careful to state that the results are not a final verdict. The group of patients who had taken steroids in the past was relatively small, and the study design means that doctors might have chosen the more effective drug for patients who already seemed like good candidates for recovery. This makes it difficult to say with absolute certainty that one factor causes the other, though the link is strong. The researchers emphasize that while the data points toward a functional test—checking if steroids help smell before starting the expensive biologic—this approach needs to be confirmed in future studies with more rigorous testing methods. For now, the study offers a hopeful but cautious guide: the ability to recover smell seems to depend less on the structural damage in the nose and more on whether the inflammation blocking the scent is reversible. This insight could help doctors and patients have more realistic conversations about the chances of regaining a lost sense of smell before committing to a year of treatment.