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Welcome to Common Ground, a podcast series discussing new research and interesting projects in the field of complementary medicine. Hello, my name is Wendy McLean, educator at vital.ly.

vital.ly is a digital platform, a professional health resource, and a distribution service all in one.

Firstly, I'd like to begin by acknowledging the Gadigal people of the Eora Nation as the traditional custodians on the land on which we gather here. I would also like to pay my respect to their elders both past and present.

Today I’ll be discussing the latest research on chronic rhinosinusitis and its complications, including its effects on mental health and cognitive function. These complications are often overlooked despite their adverse social, economic and health outcomes, and they are linked with increased disability, medical co-morbidity and reduced quality of life.

Rhinosinusitis is an inflammatory disorder of the paranasal sinuses and linings of the nasal passages. When symptoms persist for longer than 12 weeks, it is categorised as chronic. While the condition is often referred to as sinusitis, the term "rhinosinusitis" is preferred since inflammation of the sinuses rarely occurs without concurrent inflammation of the nasal mucosa.

Chronic rhinosinusitis is one of the most common chronic diseases globally, affecting about 5 to 15% of the world's population. It is a growing public health issue, and it is associated with significant economic costs, over half of which are due to productivity losses.

While the acute form is typically thought to be driven by bacterial infection causes, the chronic form are more complicated, and the pathophysiology is not fully understood. Environmental, anatomical and a host of lifestyle and co-morbidity factors may contribute to the chronic inflammation in chronic rhinosinusitis. So things like allergy, genetic predisposition, anatomical causes, as I mentioned, immunodeficiency, autoimmune conditions and even gastroesophageal reflux disease are patient related factors. And then there are the environmental factors, so your bacterial infections, viral and fungal infections, trauma, cigarette smoking, and environmental pollutants.

The clinical manifestation typically starts as nonspecific upper respiratory infection or acute sinusitis, which then fails to resolve and results in persistent symptoms. And the four cardinal symptoms include nasal obstruction, nasal discharge, facial pain and reduction or loss of smell and diagnosis is made on a minimum of two of these symptoms in conjunction with endoscopic or imaging findings. And patients may also develop nasal polyps and experience other symptoms, including cough, sleep disturbance pain, dizziness, halitosis, nasal or throat irritation.

Consistent with its underlying inflammatory etiologies, chronic rhinosinusitis is associated with other inflammatory diseases, including allergic rhinitis and asthma. In fact, it's estimated that up to 70% of patients that have it with the polyps also have co-morbid asthma and this quite often develops later in adulthood.

So the condition causes significant morbidity and disability and extensively impacts patients overall and disease specific quality of life. In addition, the impact of the disease on patients, physical and mental wellbeing is noted to be more severe than other chronic diseases, including congestive heart failure and chronic obstructive pulmonary disease.

Patients report reduced quality of life relating to their symptoms that extend beyond the sinuses, including fatigue, anxiety, depression, reduced sleep and cognitive dysfunction. And these are symptoms that should not be overlooked and they may indicate serious complications due to the anatomical relationship of the sinuses to the eyes and the brain.

So looking firstly at sleep disturbances. Up to 60 to 75% of patients who have chronic rhinosinusitis experience poor sleep which is considerably higher than the general population. And we know sleep is a critical part of overall individual health and wellness and poor sleep impacts daily performance, quality of life and mood negatively. And in patients with chronic rhinosinusitis who report poor sleep, they have significantly worse quality of life scores.

So poor sleep can be due to a number of factors. It could be the facial pain, it could be upper airway obstruction, nasal congestion, or post-nasal drip. And in addition, during sleep, this excessive nasal congestion will disrupt airflow and this causes the mouth to dry out and also increases the risk of developing obstructive sleep apnea.

And studies show that patients with both chronic rhinosinusitis who develop obstructive sleep apnea have increased inflammatory markers. And these may actually perpetuate the disease cycle and further interrupt the sleep wake cycle and also rapid eye movement sleep. In addition, obstructive sleep apnea may lead to other comorbidities, things like cardiovascular disease, metabolic syndrome, depression and neurocognitive deterioration.

Recently, chronic rhinosinusitis has been associated with an increased risk of anxiety and depression. So the prevalence of depression in the condition is reported to range from 9 to 26%. However, it is estimated that probably twice as many patients with chronic rhinosinusitis may have undiagnosed depression. So that's up to an additional or 40%.

Observational research indicates a bi-directional link between mood disorders and chronic pain. So co-morbid depression is known to contribute to chronic rhinosinusitis patients’ perception of pain significantly. And conversely, a high degree of pain is associated with an increased likelihood and severity of depression. A similar association exists between depression and sleep in the condition where sleep dysfunction is significantly associated with a history of depression. A 2017 study found that among chronic rhinosinusitis patients with significant sleep dysfunction, 82% also had comorbid moderate to severe depression and pain. Now, fortunately, both sleep and pain in these patients has been shown to improve where there has been appropriate treatment and it could also potentially help with the depression.

So one of the common underlying factors, linking pain mood and sleep disturbances is inflammation. And several studies have investigated the associations of the inflammatory cytokines involved in rhinosinusitis with mental health and quality of life. So these inflammatory markers, things like interleukin six, interferon gamma, they have been linked to depression via their effects on the central nervous system. They're also involved in pain perception. So there was a recent study that found that interleukin six was specifically elevated in patients with rhinosinusitis. And this was related to depressed mood and poor sleep quality.

Serotonin is a critical regulatory neurotransmitter in the sleep wake cycle. It also plays a crucial role in the pathobiology of depression and has been implicated in pain modulation. Now interferon gamma and some of the other cytokines that occur in rhinosinusitis have been found to reduce the availability of serotonin. Therefore, dysfunction of the serotonergic pathway may play a role in the complex interaction between pain, sleep dysfunction, and depression in these patients. However, it is an area requiring further research.

Now the complex relationships between the gut, the brain and the gut microbiota are well-researched. And we now know, that is, we have an understanding of how gut microbiota can affect health and also particularly mental health. Now the sinonasal passage also has a microbiome but its effects on disease progression and complications such as depression are less understood.

There is a recent study that was published suggesting that changes in the sinonasal microbiota, so that is dysbiosis, may actually affect neural signalling link and contribute to the mental health effect in chronic rhinosinusitis. So in this study, researchers investigated associations between the sinonasal microbiota and local concentrations of neurotransmitters, including serotonin, dopamine and GABA, and depression severity in a cohort of chronic rhinosinusitis patients compared to healthy controls.

And so they found that several commonly health associated sinonasal bacteria were positively associated with higher neurotransmitter concentrations and negatively associated with depression severity.

And what I mean by health associated bacteria, is these are the ones that are found in healthy individuals. In contrast, in depleted levels, they have been linked with things like increased rates of asthma and elevated markers of inflammation. In this study, several taxa commonly associated with an imbalanced sinonasal microbiota negatively associated with neurotransmitters and positively with depression severity.

And so, as I mentioned, chronic rhinosinusitis is characterised by multiple inflammatory parameters. And these inflammatory parameters or cytokines are known to be able to have neural effects. So they can cross the blood-brain barrier and can trigger neuroinflammatory responses that can affect brain function.

So the authors in this study also highlighted that there are increases in nasal mucosal permeability, and alterations in the microbiota which may lead to the translocation of microbial products that leads to these inflammatory processes and that could influence immunomodulation and ultimately brain function.

They found that the neurotransmitters produced within the sinonasal cavity may directly influence neural signal pathways. And this is through the nerves in, in the head, in the face. So the olfactory nerve and the trigeminal nerves.

Patients with chronic rhinosinusitis often report symptoms such as brain fog, difficulty concentrating fatigue, and poor performance. Yet these are often overlooked. And from previous studies of other inflammatory conditions, we know that there's a potential association between inflammation and cognitive decline and even dementia. Yet it's only starting to be investigated specifically in chronic rhinosinusitis. And there was a particular Japanese study that found that cognitive stores scores were significantly lower in elderly subjects with chronic rhinosinusitis than in those without. And also other studies have reported that olfactory dysfunction, which is one of the most common symptoms in chronic rhinosinusitis, is associated with dementia.

So there's several potential mechanisms that have been proposed to explain the relationship between chronic rhinosinusitis and cognitive function. Of course one of the most widely accepted is the role of inflammation and neuroinflammation in particular. Also it's recognised that chronic rhinosinusitis is associated with brain vasculopathy and stroke in epidemiological studies and could directly lead to an increased risk of vascular dementia.

So there was a recently published study that found that chronic sinus inflammation was associated with alterations in brain networks, which could potentially lead to cognitive dysfunction. So they used magnetic resonance imaging to look at the brains of individuals who had moderate to severe sinus inflammation and compared that to healthy adults with no sinus inflammation. And they found that in those with the sinus inflammation they had decreased functional connectivity within the frontal parietal network of their brains. So that's a major functional hub for modulating cognition and maintaining attention and problem solving. And they had decreased connectivity in a part of the brain called the salience network. So that's parts of the brain involved in detecting and responding to stimuli social behavior and communication. And the magnitude of the changes in the functional conductivity were associated with inflammation severity.

And we know that dysfunction of these parts of the brain have also been linked to other neuropsychiatric conditions like schizophrenia, major depression and anxiety. So basically this study showed that there were actual changes in brain activity due to the sinus inflammation, and this could explain the cognitive impairment and depression that's seen in these patients.

Now, fortunately other studies have found that with appropriate treatment these patients have had some improvement in their cognitive function.

So it is essential to understand the significance of these potential complications of chronic rhinosinusitis and the impacts on patient's quality of life.

Now complementary health practitioners have access to herbal therapeutics and nutritional and dietary interventions that will be valuable adjuncts to conventional treatments to reduce some of the underlying causes of chronic rhinosinusitis and these particular complications. So things that can help reduce inflammation, reduce oxidative stress and support the immune system.

And those will have benefits, not just for the you know, symptoms of the sinus itself, but these extra sinus symptoms. So mood, the cognition and impaired sleep. So we've got anti-inflammatory herbs, things like boswellia or curcumin and ginger and nutritional interventions such as omega three fatty acids and quercetin.

Several studies suggest that bromelain, a proteolytic enzyme derived from pineapples, may help reduce the inflammation and swelling and relieve symptoms of sinus. And it's quite commonly teamed up with the flavonoid quercetin, which has anti-inflammatory effects.

 Another potential key player is N-acetyl-cysteine (NAC). Now it can improve mucociliary clearance and it also has biofilm disrupting properties, and it has been demonstrated to protect against neutrophil dysfunction in respiratory conditions, such as cystic fibrosis. Numerous clinical studies suggest a benefit of NAC for neurological disorders and neuropsychiatric disorders because of its anti-inflammatory and antioxidant effect. So this really could be a key player and, and one that definitely needs to be investigated in clinical trials.

Now, probiotics have been well studied as interventions for targeting the gut-brain-microbiota axis for improving a range of health conditions, including mood disorders. However, there's a lack of studies looking specifically at the effects of probiotics on sinonasal inflammation and complications. There's been a couple of in vitro and animal studies, which have had positive effects or they've shown that they probiotics could prevent relapses and decreased severity of symptoms in sinonasal inflammation. There's only been a couple of human studies which have had mixed results. There was one particular study that showed oral probiotics could reduce the number of acute exacerbations for eight months.

So the key takeaways from this podcast today:

Chronic rhinosinusitis is a prevalent and debilitating inflammatory condition that affects up to one in seven people.

It can significantly reduce the quality of life in suffers and the impact on patients’ physical and mental wellbeing is noted to be more severe than other chronic diseases, including congestive heart failure and chronic obstructive pulmonary disease.

Patients report reduced quality of life relating to symptoms that extend beyond the sinuses, including fatigue, anxiety, depression, reduced sleep and cognitive dysfunction.

These symptoms are often overlooked but are quite potentially linked to the underlying inflammatory pathophysiology and despite chronic rhinosinusitis being viewed as a respiratory disorder there are underlying causes such as psychological stress, immune dysregulation and microbial dysbiosis that need to be addressed.

And the triad of chronic pain insomnia mood disorders is complex and further research is required to understand the role of this particular triad in the development and management of chronic rhinosinusitis.

So thank you very much for listening today and to our listeners, please feel free to subscribe, subscribe to Common Ground. We really do appreciate your support and feel free to leave us a review. We'd love to hear from you.