INTRODUCTION
Allergic Rhinitis (AR) is an IgE (immunoglobin-E) mediated inflammatory condition of upper airways (Hellings&Fokkens, 2006). The main clinical features involve a runny nose, sneezing, nasal congestion, nasal itching and epiphora (watery eyes) (Varshney&Varshney, 2015; Di, Lou, Ye, Miao, & Zhao, 2016). Further, additional symptoms may be sniffing, post nasal drip, impaired sense of smell and mouth breathing (Ng et al., 2000). AR is a global problem and has large variations in incidences, currently affects up to 20%-40% of the population worldwide (Soléetal., 2015; Settipane& Charnock, 2007), Europe has estimated 23% (Bauchau & Durham, 2004), and 11.03% of the Delhi population (excluding those having asthma) in India suffer from allergic rhinitis (Gaur et al., 2006).
Though not life threatening, AR symptoms are often distressing, adversely affecting the job, quality of life, and placing a burden on individuals and society (Schatz, 2007; Canonica et al., 2007). The total direct medical cost of allergic rhinitis is approximately $3.4 billion in US (Meltzer & Bukstein, 2011). Association of allergic rhinitis with asthma adds to its financial burden (Nathan, 2007). AR is highly prevalent and significantly affects the quality of life through its symptoms and comorbidities. AR has a close association with Asthma (Dara, 2017), rhinosinusitis and atopic dermatitis (Tan &Corren, 2011). Our search yielded few studies on the effect of yoga on allergic rhinitis (Chanta, A. et al., 2019; Chellaaetal, 2019). A study concluded that AR contributes 3.6 days of absenteeism per annum and unproductive 2.3 hour per workday when experiencing symptoms (Lambetal, 2006). AR symptoms may lead to both physical and mental complications. In children, it adversely affects the quality of life, sleep, and school performance and may progress to asthma causing a significant burden on his life (Meltzeretal, 2009). Immunological inflammation in AR is critically involved neural pathways thus it can impact psychological health or vice versa (Mandhane et al., 2011). Psychoneuroimmunology and medical genetics research suggest that CNS (central nervous system) may get affected by biochemical changes taking place due to allergic reactions (Marshall et al., 2002). Pharmacological treatments for AR include the use of oral intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination (Brożeketal, 2017). Immunotherapy also shows a significant reduction in symptom scores and medication use (Mueller, 2013).
Yoga intervention-based studies had document edits efficacy on upper and lower respiratory tract conditions like Allergic rhinitis (Chanta A. et al., 2019), Rhinosinusitis, Asthma and bronchitis (Shankarappa et al., 2012; Raoetal, 2014). However, there are shreds of evidence of the effectiveness of yoga intervention on conditions that coexist with Allergic Rhinitis like Asthma (Cramer et al., 2014) and rhino-sinusitis (Rastogi, 2007), Sleep difficulty (Mustianetal, 2013; Fang&Li, 2015), etc.
Yoga is a holistic way of life, which leads to bio-psychosocial and spiritual homeostasis. The root of the word yoga, is yuj which had Sanskrit origin, which means to bind or join (Distasio, 2008). Even though the primary goal of yoga is self-realization, recent studies highlight the therapeutic application of yoga for non-communicable diseases (Taneja, 2014). Traditionally, two schools of yoga are widely practiced: Raja Yoga and Hatha Yoga. The practical steps of Raja Yoga were highlighted in the form of 196 aphorisms in Patanjali Yoga sutras. Raja Yoga emphasizes more on mental purification. The Hatha yoga branch focuses on physical postures and breathing. Further Hatha Yoga School gives importance to cleansing practices called Kriyas. In the Yogic tradition of India, Hatha yoga is a considerable apparatus to prevent and overcome various disease conditions (Muktibodhanand, 1998). Sage Swatmaram in a classical text Hatha Yoga Pradipika (H.Y.P.) and sage Gherand in Gherand Samhita explains about Shatkarmas (six cleansing techniques) they are as follows Dhauti (cleansing of digestive tract), Basti (colon cleansing), Neti (Nasal cleansing), Trataka (eye cleansing), Nauli (abdominal muscle movement) and Kapalbhati (skull cleansing) (Muktibodhanand, 1998). Yogic scriptures highlight that diseases caused by an excess of mucus can be managed by Dhauti karma (Muktibodhanand, 1998). And most of the disease, which manifests above the throat can be managed by Neti-kriya. There are many yogic practices that are traditionally exercised to reduce symptoms of AR.
The emerging evidence has shown yoga as a potential alternative or complementary treatment for AR (Chanta, A. et al., 2019; Chellaa et al., 2019). Based on the recent trend in yoga, it is essential to scrutinize the application of yoga as a potential add-on therapy for AR. Hence the narrative review intended to comprehend the possible mechanisms of action of yoga in AR, the limitations of prevalent literature and direction for the future study. This review is aimed at finding the mechanism with that yoga may interfere in the pathophysiology of AR.
MECHANISMS BY WHICH YOGA MAY MODERATE THE CLINICAL SYMPTOMS OF ALLERGIC RHINITIS
1. Overview of Possible Anti-Inflammatory Mechanisms of Yoga
Recent research has elucidated some of the mechanisms underpinning the anti-inflammatory effects of yoga practices that may have an impact on reducing symptoms of allergic rhinitis (Sarubin et al., 2014) Several physiological pathways seem to mediate the anti-inflammatory effects of Yoga include – regulation of inflammatory cytokine, Hypothalamus-Pituitary-Adrenal (HPA) axis, plasma CRP level, plasma GABA level, Vagus stimulation and clearing of the nasal pathway from annoying substances through yogic cleansing techniques.
1.1. Yoga and Inflammatory cytokine
Allergic rhinitis occurs in two phases i.e. early and late; the early phase starts with the degradation of mast cells and releases histamine and tryptase resulting in localized inflammation, sneezing, itching, and rhinorrhoea, on the exposure of potential allergen to the nasal mucosa (Mandhane et al., 2011; Y. Min, 2010). Late phase caused by migration of eosinophil, mast cells, T-cells and other inflammatory cells to the nasal mucosa. These cells produce cytokines, and eosinophil produces oxygen-free radicals and hydrogen peroxide result in epithelial damage and nasal congestion (Y. Min, 2010).
Yoga-based 6-month long clinical trials on moderate asthma cases found a significant reduction in blood eosinophil count, which plays a key role in AR (Kant, 2014). Interleukin-10 (IL-10), a potent immunosuppressant, reduces inflammation in two ways; indirectly by preventing antigen-specific T-cell activation and directly by inhibiting IL-2 production from a monocyte, macrophages, Langerhans cells and dendritic cells thereby controls the expansion of T-cells (De Vries, 1995). Yoga-Based intervention for three months on 38 individuals observes an increase in anti-inflammatory cytokine IL-10, in addition study found a reduction in Pro-inflammatory Cytokine IL-12 (Cahn et al., 2017). Further, yoga intervention found to have reduced activity of the pro-inflammatory transcription factor Nuclear Factor Kappa B (NF-κB) and increased activity of the anti-inflammatory glucocorticoid receptor among breast cancer survivors (Bower et al., 2014). Furthermore, yoga-based study with 86 subjects found a reduction in Serum Interleukin-6 and Tumor Necrosis Factor [TNF]-a level in 10 days (Yadav et al., 2012). Thereby yoga has shown as a potential intervention that modulates the anti-inflammatory effect.
1.2. Yoga and HPA axis
Research has shown that the HPA axis is associated with an acute allergic inflammatory condition, and increased cytokine level activates in AR (Buske-Kirschbaum et al., 2010). Yoga has shown to be modulating the HPA axis in a number of human studies. A recent study on eight weeks of Yoga training on female patients with multiple sclerosis results shows a significant difference in serum ACTH and cortisol levels in comparison to controls (Moghadasi & Najafi, 2017). Further, a 15-day yoga-based breathing technique has shown a reduction in serum ACTH and cortisol reduction among substance abusers (Vedamurthachar et al., 2006). Furthermore, yoga intervention study on enhancement of sleep physiological, indicates higher efficiency of the HPA axis (Vera et al., 2009). The involvement of the HPA axis in the anti-inflammatory effects of Yoga was further supported by changes in levels of Salivary cortisol and Serum cortisol in yoga-based clinical trials (Michalsen et al., 2005; Raghavendra et al., 2009; Vedamurthachar et al., 2006; Yadav et al., 2012). The reduction in inflammation, mediated through the HPA axis (Ross & Thomas, 2010) may reduce nasal congestion.
1.3. Yoga and C-reactive protein (CRP) levels
CRP is a potent biomarker for inflammation, rising rapidly in inflammatory conditions (Marnell et al., 2005). Previous ten days of a yoga intervention study showed a significant reduction in plasma CRP level along with other inflammatory markers like IL-6 and TNF- α (Yadav et al., 2012). Further, 12-week Yoga intervention study on COPD patients found a marked reduction in CRP level (Arora et al., 2013). Furthermore, a study has reported that yoga reduces plasma CRP levels in patients with heart disease (Pullen et al., 2008).
1.4. Yoga and Gamma-aminobutyric acid (GABA) level
An animal study reported that GABA down regulates both T-cell autoimmunity and antigen-presenting cell (APC) activity by reducing the proliferation of reactive T cells. Thus, GABA can reduce T-cell to mediate the inflammation (Tian et al., 2011). A pilot study with 19 subjects suggests 60-minute yoga intervention enhances GABA level up to 27%, while no change observed in control (Streeter et al., 2007). A randomized control trial on 34 subjects demonstrated an increased level of thalamic GABA following 12 weeks of Yoga intervention in comparison to walking among healthy individuals (Streeter et al., 2010). Further, 12 week-long controlled intervention on MDD (Major depressive disorder) subjects reported improved GABA levels following the practice of yogasanas and pranayama (Streeter et al., 2018).
1.5. Role of Yoga on Psychological Stress and Immune mechanism
Psychological stress is another important factor that aggravates inflammation it can be objectively documented by CRP and cortisol level (Almadi et al., 2013). Biochemical changes during the allergen challenge in AR is also characterized by tiredness, malaise, irritability, and possibly neurocognitive deficits (Skoner, 2001). Evidence suggests that both stress and anxiety promote priming and hyper responsiveness to produce allergens in AR patients (Kiecolt-Glaser et al., 2009). A review on neuro inflammation suggests that neuropeptides like substance P may be released along with other inflammatory mediators and mast cells; in response to sensory nerve stimulation due to psychological stress (Black, 2002). Psychological stress kindles neuro-endocrine, sympathetic and immune response resulting in activation of the HPA axis and regulation of inflammatory mediators (Powell et al., 2013). Psychological stress has proven the role to stir up inflammation (Powell et al., 2013). Yoga has proven its role in reducing psychological stress in many clinical trials through various mechanisms. A Yoga study found increased brain alpha waves activities and serum cortisol levels following asana, pranayama and soham meditation (Kamei et al., 2000). A clinical trial on students concluded, regular practice of yoga practices may maintain physiological parameters and biomarkers of stress (Serum IFN-γ and cortisol level) following stress condition (Gopal et al., 2011). A 12-week yoga intervention study on chronic back pain sufferers revealed a significant rise in BDNF level in comparison to control (Lee et al., 2014). Yoga and meditation are capable of shifting brain execution, neurotropic and inflammatory pathways. Three-fold increase in BDNF (brain-derived neurotrophic factor) level and significant improvement in CAR (cortisol awakening response) following yoga and meditation program, suggesting an improvement in psychological parameters and rhythmicity of adrenocortical activity (Cahn et al., 2017). Pranayama (yogic breathing) decreases hyperventilation; this results in normalization of CO2 level, and reduction of bronchospasm and breathlessness. Additionally, Pranayama improves immunological parameters and reduces anxiety (Sankar & Das, 2018).
1.6. Yoga and Neurogenic Inflammation
When nerve endings come in contact with cytotoxins released by inflammatory cells (Eosinophil & Mast cells) it leads to excitation of the both afferent and efferent nerve pathways this makes to secrete neuropeptides, including Substance P and Neurokine A, (Togias, 2000). In response to these neuropeptides, adjacent mast cells release histamine. Histamine, in turn, evokes neuropeptide release, this exhibits a bidirectional link (Rosa & Fantozzi, 2013), and this is called neurogenic inflammation. It results in plasma extravasation and glandular secretion (Tai & Baraniuk, 2002). The sensation of pain and stiffness also developed due to the involvement of nasal sensory nerves (Tai & Baraniuk, 2002). A recent study in pediatric settings with mind-body therapy to evaluate its effect on neuropeptides (calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP)), could not find any significant difference, possibly due to inadequate sample size (Gershan et al., 2015). We do not find any yoga intervention study to evaluate its role in modulating neuropeptides. Yoga reduces cells of inflammation (Kant, 2014) those are responsible for cytokine secretion thereby initiates a cascade of Neurogenic Inflammation, so it has been proposed that the practice of yoga reduces neurogenic inflammation; however, no direct experimental confirmation is currently available.
1.7. The cholinergic anti-inflammatory pathway
Inhibition of pro-inflammatory cytokines and systemic inflammation through efferent vagal is termed as “The cholinergic anti-inflammatory pathway” (Czura & Tracey, 2013). Electrical stimulation of vagus nerve may suppress both local and systemic inflammation (Martelli et al., 2014). A clinical trial with an objective to assess the role of yoga on autonomic nervous system found the well-balanced beneficial activity of vagal efferent among the yoga groups (Muralikrishnan et al., 2012). Researchers reported that relaxation by Iyengar Yoga practice increases cardiac vagal modulation in healthy yoga practitioners (Khattab et al., 2007). This provides an insight on physiological mechanism for immunomodulation through the motor branches of the vagus nerve, and CNS control of peripheral inflammatory responses.
2. Yoga and Hyper-responsiveness in AR
Hyper-responsiveness of airways is closely related to an IgE mediated allergic inflammatory condition (Sears et al., 1991). Chronic exposure to allergens in AR can lead to hyper-responsiveness of the nasal mucosa (Baraniuk & Kim, 2007). Airway hyper-responsiveness also may be due to airway inflammation, airway remodeling and abnormalities of smooth muscles and neural control (Berend et al., 2008). Neurotrophins, such as the NGF (Nerve Growth Factor) are the mediators of neural hyper-responsiveness (Togias, 2000). Yoga has a calming effect on the mind, the devotional sessions that help to harness the emotional upsurges are particularly useful in eliminating emotional stresses (Nagendra & Nagarathna, 1986). Yogic SuddhiKriya like Neti clear nasal pathway from allergens and other annoying substances (Rabone & Saraswati, 1999) that can reduce the number of inflammatory cells and cytokine levels in the nasal mucosa which may result in lessening of hyper-responsiveness. This signifies that yoga induces a greater degree of physiological relaxation and reduces hyper-responsiveness.
3. Effect of Yogic <italic>Shuddhi Kriyas</italic> in reducing allergen and inflammatory mediators
Roots of nasal irrigation are in ancient yogic purification technique involves Neti Kriya (nasal cleansing), there are two types of Neti; JalaNeti, i.e nasal irrigation with lukewarm saline water and Sutra Neti, i.e cleaning of the nasal path with a thread or catheter. Neti removes foreign bodies like allergens and dust from the nasal passage (Muktibodhanand, 1998). There are sufficient studies available that show the positive effect of nasal irrigation on nasal symptom scores (Tomooka et al., 2000; Rabone & Saraswati, 1999). A recent review study suggests that JalaNeti (yogic nasal cleansing techniques) and Pranayama (Yogic breathing) have a therapeutic effect for people suffering from AR including asthma (Agnihotri, et al., 2016). A 10-week long clinical trial with the daily practice of saline nasal spray significantly reduced symptoms of nasal symptoms and episodes of rhinitis (Tano&Tano, 2004). JalaNeti helps in preventing upper respiratory tract diseases equally in adults and children (Meera et al., 2019). Nasal lavage with isotonic seawater shown significant improvement in mucociliary clearance, Nasal Peak Expiratory Flow (NPEF) and nasal symptoms such as obstruction, posterior secretions, itching, irritation and sneezing (Holmström, et al., 1997). A single case study reported the beneficial results of Sutra Neti in his snoring and sleep apnoea condition (Ramalingam & Smith, 1990). A review study found saline nasal irrigation a safe procedure for both adults and children. It is helpful in flushing and moisturizing the nasal cavity also promotes mucociliary clearance (Papsin, & McTavish, 2003). A clinical trial with thirty allergic rhinitis patients underwent saline nasal irrigation and heated water vapor at 43 and 41°C, at different points of time, results revealed that saline nasal irrigation significantly reduces histamine concentration from nasal secretion (Georgitis, 1994). Another clinical trial on pediatric subjects for 12 weeks reported a significant reduction in AR symptoms and Eosinophil count (Chen et al., 2014).
3.1. Mechanism of action for <italic>Neti</italic>
The mechanism of action of JalaNeti or nasal irrigation can be understood in four ways. 1. Direct physical cleansing by flushing out thick mucus, crusts, debris, allergens, air pollutants (Blake & McTavish, 2003; Rabone & Saraswati, 1999).
2. The removal of inflammatory mediators (Georgitis, 1994; Chen et al., 2014).
3. Better mucociliary clearance by improving ciliary beat frequency (Holmström et al., 1997).
4. Desensitization of Nasal Mucosa - Yogic cleansing techniques Kriyas may desensitize the vagal end receptors by systematic exposure to nonspecific graded irritants followed by deep relaxation (Nagendra & Nagarathna, 1986).
4. A Proposed Model for the Mechanism of Yoga therapy in Allergic Rhinitis
Given the multifaceted discussion on pathways in allergic inflammation, it is hypothesized that yoga might exert anti-inflammatory actions in allergic rhinitis in the following ways: The local effect by improving mucociliary clearance, reducing inflammatory cytokines and inflammatory cells in the nasal mucosa. Further, the general effect mediated through the HPA axis, Efferent vagal stimulation, CRP level, and GABA. Yoga has shown improvement on Lung capacity and nasal airflow in AR patients. If yoga can be shown to have these actions on modulating cytokines and other pathways potentially mediating inflammation, then these modulations would be expected to be correlated with improvements in clinical signs and symptoms, including a reduction in rhinorrhea, sneezing and nasal obstruction. This review integrates current approaches and scientific evidence to illustrate how practicing traditional factors of yoga helps in the management of Allergic Rhinitis.
CONCLUSION
Yoga has recently emerged as having health benefits in allergic and other chronic conditions, yet yoga has not been systematically evaluated as therapy for AR. Evidence support that yoga reduces inflammation by modulating inflammatory mediators in some studies for conditions other than allergic rhinitis. Further, pieces of evidence support that yoga reduces nasal congestion, improves lung capacity, improve nasal airflow and symptom score in allergic rhinitis cases. Few studies reported Netikriya (yogic nasal cleansing) and a similar technique, saline nasal irrigation was effective in reducing symptoms of allergic rhinitis. Role of yoga in modulating neuropeptides like SP, CGRP, and VIP, and Neurotrophins NGF and BDNF had to be studied as they are shown to contribute in the early and late phases of AR respectively. Therefore, it is suggested in our proposed model that, yoga may downregulate certain inflammatory and pro-inflammatory cytokines. Furthermore, yoga up-regulates anti-inflammatory interleukins. Yoga, a mind-body therapy, embraces a holistic model of health and well-being. Yoga not only focuses on cardinal symptoms of AR but may also reduce psychological stress and sleep difficulty. Yoga may also reduce the hyper-responsiveness of nasal airway by improving sympathovagal balance. The delimitations of the present review include restricting the search to open online databases, which might narrow the access to substantial research work done in the domain. Furthermore, the prevailing review is constrained to the narrative in nature, and statistical accountability was not presented. Current review highlights the importance of integrating yoga-based interventions as add-on therapy for AR. Further, there is a need for large scale, long-term effect, systematic study with augmented methodological designs to comprehend the potential neurobiological mechanisms of yoga-based intervention in patients with Allergic Rhinitis is needed.