The Overlooked Symptom: olfactory Dysfunction in Cystic Fibrosis

While the pulmonary complications of cystic fibrosis (CF) are well-documented, a French research team has brought to light another important symptom often overlooked: a diminished or altered sense of smell. Studies suggest that between 12% and 71% of CF patients experiance olfactory dysfunction, which clinicians often attribute to chronic sinus inflammation. However, groundbreaking research from the National Institute for Research for Agriculture, Food and the Surroundings (INRAE), in collaboration with Inserm, CNRS, and various European universities, reveals a more direct connection: the defective CFTR gene itself.

We observed that 80% of a small group of ten individuals exhibited an altered sense of smell.pablo Chamero, INRAE Biologist

This revelation could revolutionize how we understand and manage cystic fibrosis, potentially leading to targeted therapies that address not only the respiratory issues but also the sensory deficits that considerably impact patients’ well-being.

Decoding the Olfactory Impact: A Multi-Faceted Approach

To investigate the genetic influence on olfaction,researchers employed a combination of molecular analyses and functional tests,including the Sino-Nasal Outcome Test-22 (SNOT-22),a standard clinical questionnaire for hyposmia (reduced ability to smell). Their findings revealed a distinct difference in the distribution of olfactory receptors in CF patients compared to individuals without the mutation. Furthermore,patients exhibited a reduced number of globular basal cells,which are crucial for the regeneration of olfactory tissues.

According to recent data from the Cystic Fibrosis Foundation Patient Registry, over 30,000 people in the United States are living with CF. Understanding the full spectrum of symptoms, including olfactory dysfunction, is crucial for providing comprehensive care.

Animal Models Validate the Genetic Link

To further solidify the link between the genetic alteration and olfaction, the research team turned to an animal model. classic models, in mouse or rat are not suitable for cystic fibrosis. Animals do not have the same symptoms as humans. Pork is closer to humans, both anatomically and genetically. And we were able to measure the fault of olfaction in new born pigs, the researchers stated.By studying newborn pigs with CF, they were able to avoid the confounding effects of chronic bronchial inflammation and isolate the direct impact of the CFTR gene on olfactory function.

Future directions: Exploring the Therapeutic Potential

By integrating clinical data with animal studies, the researchers observed a clear correlation between the CFTR gene mutation and altered expression of olfactory receptors.This raises the question: do CF patients experience the world through a different sense of smell? This is the focus of their ongoing research.

While this research doesn’t promptly offer a therapeutic solution, it sheds light on the diverse range of symptoms associated with cystic fibrosis. The sensory involvement, in particular, holds significant therapeutic potential. Studies conducted during the COVID-19 pandemic demonstrated that olfactory dysfunction is linked to a decline in quality of life,and anosmia (complete loss of smell) has even been associated with depression. These findings underscore the importance of addressing this symptom in CF patients.

The COVID-19 pandemic highlighted the profound impact of smell loss on mental health and overall well-being.A study published in JAMA Network Open found that individuals with persistent smell loss after COVID-19 were more likely to experience symptoms of depression and anxiety.

No Conflicts of Interest Declared

Pablo Chamero has declared no conflicts of interest related to this research.