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Strong humming for one hour daily to terminate chronic rhinosinusitis in four days: A case report and hypothesis for action by stimulation of endogenous nasal nitric oxide production
Abstract
Rhinosinusitis is an inflammation or infection of the nose and air pockets (sinuses) above, below and between the eyes which connect with the back of the nose through tiny openings (ostia). Rhinosinusitis can be caused by bacteria, viruses, fungi (molds) and possibly by allergies. Chronic rhinosinusitis (CRS) is an immune disorder caused by fungi. The immune response produced by eosinophils causes the fungi to be attacked, which leads to damage of the sinus membranes, resulting in full-blown rhinosinusitis symptoms. Gaseous nitric oxide (NO) is naturally released in the human respiratory tract. The major part of NO found in exhaled air originates in the nasal airways, although significant production of NO also takes place in the paranasal sinuses. Proper ventilation is essential for maintenance of sinus integrity, and blockage of the ostium is a central event in pathogenesis of sinusitis. Concentrations of NO in the healthy sinuses are high. Nasal NO is known to be increased 15- to 20-fold by humming compared with quiet exhalation. NO is known to be broadly antifungal, antiviral and antibacterial. This case report shows that a subject hummed strongly at a low pitch ( approximately 130 Hz) for 1h (18 hums per minute) at bedtime the first night, and hummed 60-120 times 4 times a day for the following 4 days as treatment for severe CRS. The humming technique was described as being one that maximally increased intranasal vibrations, but less than that required to produce dizziness. The morning after the first 1-h humming session, the subject awoke with a clear nose and found himself breathing easily through his nose for the first time in over 1 month. During the following 4 days, CRS symptoms slightly reoccurred, but with much less intensity each day. By humming 60-120 times four times per day (with a session at bedtime), CRS symptoms were essentially eliminated in 4 days. Coincidentally, the subject's cardiac arrhythmias (PACs) were greatly lessened. It is hypothesized that strong, prolonged humming increased endogenous nasal NO production, thus eliminating CRS by antifungal means.
... Advice given to patients to make a dedicated and persistent effort to maintain nasal breathing might in some cases help to break the cycle that perpetuates nasal obstruction by improving mucosal homeostasis and the regulation of innate immune pathways (Gelardi et al., 2012;Lane, 2009). Other protocols include general breathing training aimed at optimizing breathing patterns and reducing hyperventilation (Bartley, 2006), with some using localized nasal muscle training, humming, nasal hygiene instructions and oronasal exercises such as breath holding either as stand-alone techniques or in conjunction with general breathing training (Eby, 2006;Levrini et al., 2014;Vaiman et al., 2005). These studies provided the foundations for further development of clinical protocols for nasal rehabilitation. ...
... The practical elements of the protocol included techniques such as humming (Eby, 2006), smell training (Hilgers et al., 2002), nasal muscle training (Vaiman et al., 2005) and breath holding (Hasegawa et al., 1978). These techniques were combined into a structured protocol that also included novel techniques such as the nose opening smile (NOS) (Appendix A), mindfulness of nasal breathing, as well as instructions on humming and nasal muscle training variations. ...
... The reduction in nasal symptoms and improved ability to breathe nasally are consistent with anecdotal reports and previous research on other protocols with some similarities to the FNBR program used here (Bartley, 2006;Eby, 2006;Vaiman et al., 2005;Villa et al., 2015). In Bartley's (2006) case series, patients who were nonresponsive to multiple surgical and medical interventions improved after undertaking a course of physiotherapist-led breathing retraining. ...
p> Purpose: Nasal disuse and mouth breathing are associated with negative structural, functional, postural, occlusal, and behavioural changes. While there is some research to suggest that nasal breathing exercises can reduce mouth breathing, clinical protocols have not been extensively investigated. The purpose of this research was to determine the feasibility and effectiveness of a nasal breathing rehabilitation protocol based on Integrative Breathing Therapy principles called Functional Nasal Breathing Rehabilitation (FNBR).<p
... Advice given to patients to make a dedicated and persistent effort to maintain nasal breathing might in some cases help to break the cycle that perpetuates nasal obstruction by improving mucosal homeostasis and the regulation of innate immune pathways (Gelardi et al., 2012;Lane, 2009). Other protocols include general breathing training aimed at optimizing breathing patterns and reducing hyperventilation (Bartley, 2006), with some using localized nasal muscle training, humming, nasal hygiene instructions and oronasal exercises such as breath holding either as stand-alone techniques or in conjunction with general breathing training (Eby, 2006;Levrini et al., 2014;Vaiman et al., 2005). These studies provided the foundations for further development of clinical protocols for nasal rehabilitation. ...
... The practical elements of the protocol included techniques such as humming (Eby, 2006), smell training (Hilgers et al., 2002), nasal muscle training (Vaiman et al., 2005) and breath holding (Hasegawa et al., 1978). These techniques were combined into a structured protocol that also included novel techniques such as the nose opening smile (NOS) (Appendix A), mindfulness of nasal breathing, as well as instructions on humming and nasal muscle training variations. ...
... The reduction in nasal symptoms and improved ability to breathe nasally are consistent with anecdotal reports and previous research on other protocols with some similarities to the FNBR program used here (Bartley, 2006;Eby, 2006;Vaiman et al., 2005;Villa et al., 2015). In Bartley's (2006) case series, patients who were nonresponsive to multiple surgical and medical interventions improved after undertaking a course of physiotherapist-led breathing retraining. ...
p> Purpose: Nasal disuse and mouth breathing are associated with negative structural, functional, postural, occlusal, and behavioural changes. While there is some research to suggest that nasal breathing exercises can reduce mouth breathing, clinical protocols have not been extensively investigated. The purpose of this research was to determine the feasibility and effectiveness of a nasal breathing rehabilitation protocol based on Integrative Breathing Therapy principles called Functional Nasal Breathing Rehabilitation (FNBR).<p
... 17,18 In the present Breath Powered device, it is postulated that the oscillating capsule and airflow may significantly enhance exchange of air in upper narrow parts of the nose, as in part observed in response to humming and pulsating nebulizers. 45,46 In addition, there are reasons to hypothesize that potential positive effects mediated by the positive air pressure, rapid vibrations produced by the rattling capsule, and the removal of NO may all play a role in alleviating migraine headache. 46,47 One or more of these, or other, device-related mechanisms may contribute to the high response rate in the placebo groups in the trials with Breath Powered powder delivery in migraine patients. ...
... 45,46 In addition, there are reasons to hypothesize that potential positive effects mediated by the positive air pressure, rapid vibrations produced by the rattling capsule, and the removal of NO may all play a role in alleviating migraine headache. 46,47 One or more of these, or other, device-related mechanisms may contribute to the high response rate in the placebo groups in the trials with Breath Powered powder delivery in migraine patients. ...
The nose offers an attractive noninvasive alternative for drug delivery. Nasal anatomy, with a large mucosal surface area and high vascularity, allows for rapid systemic absorption and other potential benefits. However, the complex nasal geometry, including the narrow anterior valve, poses a serious challenge to efficient drug delivery. This barrier, plus the inherent limitations of traditional nasal delivery mechanisms, has precluded achievement of the full potential of nasal delivery. Breath Powered bi-directional delivery, a simple but novel nasal delivery mechanism, overcomes these barriers. This innovative mechanism has now been applied to the delivery of sumatriptan. Multiple studies of drug deposition, including comparisons of traditional nasal sprays to Breath Powered delivery, demonstrate significantly improved deposition to superior and posterior intranasal target sites beyond the nasal valve. Pharmacokinetic studies in both healthy subjects and migraineurs suggest that improved deposition of sumatriptan translates into improved absorption and pharmacokinetics. Importantly, the absorption profile is shifted toward a more pronounced early peak, representing nasal absorption, with a reduced late peak, representing predominantly gastrointestinal (GI) absorption. The flattening and "spreading out" of the GI peak appears more pronounced in migraine sufferers than healthy volunteers, likely reflecting impaired GI absorption described in migraineurs. In replicated clinical trials, Breath Powered delivery of low-dose sumatriptan was well accepted and well tolerated by patients, and onset of pain relief was faster than generally reported in previous trials with noninjectable triptans. Interestingly, Breath Powered delivery also allows for the potential of headache-targeted medications to be better delivered to the trigeminal nerve and the sphenopalatine ganglion, potentially improving treatment of various types of headache. In brief, Breath Powered bi-directional intranasal delivery offers a new and more efficient mechanism for nasal drug delivery, providing an attractive option for improved treatment of headaches by enabling or enhancing the benefits of current and future headache therapies.
... Beyond the above points, the additional possibilities may include increased air exchange in the lung during simple Bhramari due to increased nitric oxide levels during the humming process [7,[17][18][19]. Several studies have highlighted that HRV parameters improve during meditation [20,21]. ...
Objective
In this study, our goal was to understand the comparative impact of humming, physical activity, emotional stress, and sleep on several heart rate variability (HRV) parameters, including the stress index (SI), and to assess the effectiveness of humming (simple Bhramari) as a stress buster based on the HRV parameters.
Methods
This pilot study assessed the long-term HRV parameters of 23 participants in terms of four activities: humming (simple Bhramari), physical activity, emotional stress, and sleep. The single-channel Holter device measured the readings, and data was analyzed using Kubios HRV Premium software for time and frequency-domain HRV parameters, including the stress index. Regarding statistical analysis, single-factor ANOVA followed by paired t-test was used to compare the results of HRV parameters "during" the four activities to understand if humming generates the outcome to enhance the autonomic nervous system.
Results
Our findings revealed that humming generates the lowest stress index compared to all three other activities (physical activity, emotional stress, and sleep). Several additional HRV parameters also supported the positive impact on the autonomic nervous, equivalent to stress reduction.
Conclusions
Humming (simple Bhramari) can be an effective stress-buster based on the assessment of several HRV parameters during its practice and in comparison with other activities. A regular daily humming routine can help enhance the parasympathetic nervous system and slow down sympathetic activation.
... It is estimated that humming increases the endogenous generation of NO level by 15-fold as compared with the quite exhalation. [31] Pranava Pranayama, having a component of humming in it, enhances the expression of NO, increases carbon dioxide output by extended exhalation and alkaline pH preventing coagulopathies and morbidity. NO improved severe hypoxia and shortens the period of hospital stay and also increases the survival rate. ...
... 71 RB practiced with Khechari, Shanmukhi Mudras, mental visualization, and external-internal breath retentions may increase CO 2 levels and 15 times more endogenous NO than quiet exhalation. 72 Elevated NO and CO 2 act as anti-inflammatory and antimicrobial agents to overcome the infection, relax bronchial tree smooth muscles, and improve the ventilation-perfusion ratio and breathlessness. 73 The practice of PL and EASL stimulates external anal sphincter (EAS), ischiocavernosus, bulbospongiosus, transverse perineal muscles, the urethral sphincter, and the pelvic diaphragm, 74 especially pudendal nerve fibers to set the parasympathetic tone. ...
Background and Purpose
About 56% of symptomatic COVID-19 survivors have been found with neuropsychological comorbidities, such as depression, anxiety, posttraumatic stress disorders (PTSD), and impaired quality of life (QoL). Alongside, antimicrobial, anti-inflammatory, neuroprotective, regenerative, immunomodulatory, cardio-pulmonary health promotive, and psychological benefits of yogic and Ayurvedic intervention are well documented. Therefore, this study aimed to assess the effect of online Yoga (OYI) and Yoga cum Ayurveda intervention (OYAI) on COVID-19-induced depression, anxiety, PTSD, and poor QoL.
Method
Seventy-two participants (males/females: 33/26) with at least a 3-month back history of symptomatic COVID-19 infection and age (mean ± SD: 32.33 ± 9.9 and 33.04 ± 12.9 for males and females, respectively) were recruited from Patanjali Ayurveda Hospital, Haridwar, India, and All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India, before random allocation into an equal-sized control group (CG), Yoga group (YG) and Yoga cum concoction (YCG) group. Split-plot analysis of variance and Kruskal–Wallis tests with Bonferroni adjusted post hoc comparisons were computed for normal and nonnormal data using IBM SPSS (25th Version, SPSS South Asia Private Limited, Bangalore, India).
Results
Both the treatments—the 30-day OYI and OYAI, significantly improved depression ( P < .002, ES: -0.99 and P < .001, ES: -2.11), anxiety ( P < .001, ES: -1.32 and -1.89), PTSD ( P < .001, ES: -1.8 and -1.83) and QoL related constructs ( P < .001, ES: 0.63 and 0.76; 0.71 and 0.93 for each OYI and OYAI versus general health and physical health; P < .001, ES: 0.65 for OYAI versus psychological health; and P < .003, ES: 0.54 for OYI versus environment) of the participants compared to the controls.
Conclusion
OYAI may better ameliorate COVID-19-induced psychological comorbidities than OYI with no adverse effects.
... 30 The last study in this category was a case report of a patient who utilized humming as a CRS treatment strategy and is described in Table 1. 31 ...
Background:
Acoustic energy and vibration therapy are emerging as helpful adjuncts across many disease states. There has been interest in how this technology can either serve as an alternative treatment or enhance delivery of medications to treat pathology within the nasal cavity and paranasal sinuses. Our objective was to perform a scoping review of the state of the science of vibration treatment used in sinonasal disease.
Methods:
A search of Embase, Pubmed and CINAHL databases was performed in November 2021. Included studies evaluated acoustic energy as a means of treatment in sinonasal diseases. Datapoints collected included type of technology utilized, disease state treated and outcomes.
Results:
The initial search identified 2902 studies, of which 44 met inclusion criteria. A wide array of vibrational technology such as ultrasound, sonic aerosols or phonophoresis, with varying frequency and amplitude were described. 26 studies evaluated the use of acoustic energy to treat sinonasal disease itself, while 18 studies evaluated the use of acoustic energy to facilitate drug delivery to the sinonasal cavity. Outcome measures across studies were highly varied.
Conclusions:
Vibration technology used in patients with sinonasal pathology has been shown to improve pain, sinonasal symptoms and radiologic outcome measures in small studies. Given the heterogeneous study populations and outcomes, no conclusion could be reached regarding overall effectiveness of acoustic energy as a primary treatment. Further research is required to study specific treatment indications in larger patient populations to fully understand the potential clinical benefit and to determine optimal therapeutic characteristics of sound energy. This article is protected by copyright. All rights reserved.
... Sinuses generate NO and release it to the nose. 89,91 As aforementioned, NO has antifungal, antiviral, antibacterial, and anti-inflammatory effects, and therefore plays an essential part in sustaining the health and functions of the airway. Interference with this endogenous nasal nitric oxide production and release can further aggravate the symptoms. ...
The nose is the initial site of viral infection, replication, and transmission in the human body. Nasally inhaled vaccines may act as a promising alternative for COVID-19 management in addition to intramuscular vaccination. In this review, the latest developments of nasal sprays either as repurposed or antiviral formulations were presented. Nasal vaccines based on traditional medicines, such as grapefruit seed extract, algae-isolated carrageenan, and Yogurt-fermenting Lactobacillus, are promising and under active investigations. Inherent challenges that hinder effective intranasal delivery were discussed in detail, which included nasal device issues and human nose physiological complexities. We examined factors related to nasal spray administration, including the nasal angiotensin I converting enzyme 2 (ACE2) locations as the delivery target, nasal devices, medication translocation after application, delivery methods, safety issues, and other nasal delivery options. The effects of human factors on nasal spray efficacy, such as nasal physiology, disease-induced physiological modifications, intersubject variability, and mucociliary clearance, were also examined. Finally, the potential impact of nasal vaccines on COVID-19 management in the developing world was discussed. It is concluded that effective delivery of nasal sprays to ACE2-rich regions is urgently needed, especially in the context that new variants may become unresponsive to current vaccines and more refractory to existing therapies.
... Humming act as a sonic cleanser and cures the infection of respiratory tract by decreasing the swelling of sinus ostea resulting into better drainage and oxygenation. [33] Humming exercise also increases the vital capacity. It is estimated that humming increases the endogenous generation of nitric oxide level by 15-fold as compared with the quite exhalation. ...
Objective: For maintaining sound physical and mental health it is extremely beneficial for mankind to do pranayama. Prāṇāyāma bring about varying physiological and psychological effects. Pranayama is a branch of yoga practice and also considered as the fourth limb of ancient aṣṭāṅga yoga consisting of breathing techniques. This article aims to attain an insight on the effectiveness of Bhramari Pranayama (Bhr.P) on health and explores its need to be implemented in day to day life as a routine by all individuals in current covid 19 pandemic. Data source: The studies done in previous years were found using Medline, Embase, Google scholar, pub med and manual search. Studies conducted on the health effectiveness of Bhramari Pranayama specifically were included in this study. Review methods: It has been tried to keenly understand the role of Bhramari pranayam in particular and exploring some new concepts related to it in this review. Features of Bhramari Pranayama are dealt in detail with its potential effects on various systems of human body and its potentiality as a therapy tool. Result and conclusion: In the studies incorporated, the Bhramari pranayam practices have shown para-sympathetic dominance. There are some uplifting effects of Bhramari pranayam on different physiological systems. In holistic yoga therapy schedule pranayama is also an integral component which involves slowing down of the normal breathing rate along with an internal awareness and conscious inner focus on the respiration and reduces stress which finally causes improvement in ailments due to covid 19 pandemic.
... Understanding the CRS pathophysiology may offer better diagnostic techniques and permit the development of new treatment strategies. The contribution of nitric oxide (NO) in CRS is discussed in the current literature [12][13][14]. Vlad et al. [15] assessed the arginase (ARG) expression in the mucosa of CRS patients. Increased ARG concentration can decrease NO levels by lessening the accessibility of its precursor, L-arginine. ...
Chronic rhinosinusitis (CRS) is one of the most common chronic medical conditions worldwide, affecting all age groups. [...]
... Humming exercise also increases the vital capacity. It is estimated that humming increases the endogenous generation of nitric oxide level by 15-fold as compared with the quite exhalation [8]. Hypoxia in ARD Syndrome leads to blood coagulation by depression of body defence anticoagulatory and fibrolytic properties along with metabolic acidosis. ...
The Coronavirus (2019-Cov-2) infection Covid-19 is highly contagious caused by single stranded RNA virus (+ssRNA) with nucleocapsid and spreading widely all across the world and responsible for more than 3.6 million morbidity and 0.25 million mortality No specific treatment is available till date. The clinical symptoms are mainly upper respiratory leading to diffuse viral pneumonia and multiple organ failure involving. Kidney, Liver and Heart along with coagulopathies. During 2004 (SARS-CoV) pandemic role of nitric oxide in its management is well demonstrated. Nitric Oxide (NO) reversed pulmonary hypertension. Improved severe hypoxia and shortened the stay in ICU and ventilatory support. Nitric Oxide increased the survival rate. The genetic composition of Corona Virus (SARS-CoV) is almost similar to Covid-19, thus indicates good chances of effectiveness or enhancement in results by Nitric Oxide along with other modes in treatment of Covid-19. It has been proved by studies by serendipity humming increases NO Expression dramatically.It is estimated that humming increases the endogenous generation of nitric oxide level by 15-fold. Hypoxia in ARD Syndrome leads to blood coagulation by depression of body defence anticoagulatory and fibrolytic properties along with metabolic acidosis. If we go into hypoxic hypercapnic state no hyper coagulation takes place. Hence Bhramari by enhancing the expression of Nitric Oxide and increased Carbon dioxide by extended exhalation and alkaline pH prevents coagulopathies and morbidity due to Covid-19.
... Lately, nitric oxide (NO) has gained a central role in local chronic inflammatory reactions. The paranasal sinuses are considered a major source of NO that is held to ensure a protective role for the upper (antibacterial, antiviral, antifungal, increases mucociliary clearance and modulates inflammatory response) [3][4][5] and lower airways [5]. Nasal NO levels have been reported to be low in patients with chronic [4,6] or acute rhinosinusitis [7] and primary ciliary dyskinesia [8], but high in allergic rhinitis [9]. ...
Nitric oxide (NO) has emerged as an important regulator of upper airway inflammation, mainly as part of the local naso-sinusal defense mechanisms. Increased arginase activity can reduce NO levels by decreasing the availability of its precursor, L-arginine. Chronic rhinosinusitis (CRS) has been associated with low levels of nasal nitric oxide (nNO). Thus, the present study investigates the activity of arginase I (ARG1) and II (ARG2) in CRS and its possible involvement in the pathogenesis of this disease. Under endoscopic view, tissue samples of pathologic (n = 36) and normal (n = 29) rhinosinusal mucosa were collected. Arginase I and II mRNA levels were measured using real-time PCR. Our results showed low arginase I activity in all samples. The levels of ARG2 were significantly higher in patients with chronic rhinosinusitis compared to the control group (fold regulation (FR) 2.22 ± 0.42 vs. 1.31 ± 0.21, p = 0.016). Increased ARG2 expression was found in patients with CRS without nasal polyposis (FR 3.14 ± 1.16 vs. 1.31 ± 0.21, p = 0.0175), in non-allergic CRS (FR 2.55 ± 0.52 vs. 1.31 ± 0.21, p = 0.005), and non-asthmatic CRS (FR 2.42 ± 0.57 vs. 1.31 ± 0.21, p = 0.028). These findings suggest that the upregulation of ARG2 may play a role in the pathology of a distinctive phenotype of CRS.
... There are several mechanism by which humming is supposed to relieve the symptoms of sinusitis. The first mechanism as described by Eby [15] is that humming acts as a sonic cleanser. Humming creates sound vibrations that encourage air to move back and forth between the sinuses and nasal passage. ...
Introduction
A multitude of modalities are available for the treatment of chronic rhinosinusitis, however, each has its side effects and compliance issues. Bhramari pranayama, which is a breathing exercise in the practice of yoga, offers an inexpensive and free from side effect modality in this regard.
Objective
The objective of this study was to evaluate the efficacy of Bhramari pranayama in relieving the symptoms of chronic sinusitis.
Methodology
A total of 60 patients with chronic sinusitis were randomly divided into two groups, one received conventional treatment of chronic sinusitis and the other group was in addition taught to practice yogic breathing exercise Bhramari pranayama. The patients were advised to practice this breathing exercise twice a day and were followed up at 1, 4, and 12 weeks using the Sino-Nasal Outcome Test (SNOT-22 score).
Results
The mean SNOT-22 score in the group following the Bhramari pranayama breathing exercise using the ANOVA test improved from 39.13 ± 9.10 to 24.79 ± 8.31 (P = 0.0002), this improvement was seen by the end of 4 weeks itself and continued until the 12th week of assessment.
Conclusion
Integrating regular practice of Bhramari pranayama along with the conventional management of chronic rhinosinusitis is more effective than conventional management alone.
... It is estimated that humming increases the endogenous generation of NO level by 15-fold as compared with the quite exhalation. [7] Because of its vasodilator effect, NO can control the filling of nasal capacitance vessels, thus nasal airflow, nasal mucosal temperature, and humidification, hence providing air conditioning to sinuses and respiratory passage. This, in turn, affects the ciliary flow and cleansing of the nose, paranasal sinuses, including nasopharyngeal tubes. ...
The World Health Organization (WHO) estimates, aging populations is on the increase in developing countries and along with modernization, deafness, and dementia is going to become epidemic which warrants early intervention to prevent this almost incurable diseases. The preventive measures barely exist in and adopted by the society our country.
The deafness which is one of the most common etiological factors precipitating dementia. Out of 738 crore world population, 36 crore suffer from hearing disability, which is more than 40 dB hearing loss. The WHO estimates that in 2025 there will be 1.2 billion people over the age of 60 years worldwide suffer by presbyacusis.[1],[2] Almost 50% of senior citizens above the age of 75 years suffer from disabling hearing loss.[3] Only 20% of these senior citizens are benefitted with the hearing aid.[4] The hearing loss leads to isolation, depression, and dementia.
Dementia is the general term use to express a decline in mental ability severe enough to interfere with daily life. The person has problem in speaking, orientation of place, lose goods, having mood, and personality changes.
The incidence of Alzheimer's diseases varies in India from 4.7% to 5.34% in senior citizens which is going to increase almost 4 times in next two decades. Hence, we have to identify examine and document the population above the age of 50 years having or prone to hearing impairment to prevent this epidemic of deafness leading to dementia and Alzheimer's diseases.
There is no significant treatment or cure of old age deafness (presbyacusis) or of dementia in modern medicine. The prevention of deafness by Yoga, lifestyle changes including diet and avoiding ototoxic drugs and chemicals may play a big role in it.[5]
Yoga is an ancient discipline to maintain or to bring health to the physical, mental, spiritual, and emotional dimensions of the individual. The National Institutes of Health (USA) has classified yoga as a form of complementary and alternative medicine and considered as a holistic approach to physical and mental health.
Cervical and shoulder exercise, Bhramari Pranayama in Shanmukhi Mudra, Kumbhaka along with Gyan Mudra and Shunya Mudra may play a significant role in prevention. A person of any age in standing, sitting, or lying down position even on a hospital bed can perform humming exercise. A phonatory respiratory exercise releases nitric oxide (NO). NO is a gas molecule, key biological messenger playing an important role in biological processes at the cellular level. Humming (Bhramari) increases the production of NO from sinuses, nasal mucosa, and blood vessels.
NO contributes to nonspecific host defense against bacterial, viral, fungal, and parasitic infections, hence takes care of infection in the body. NO improves ventilation–perfusion ratio in the lung along with the relaxation of bronchial tree smooth muscles; hence, oxygen uptake is increased and provides relief in bronchial asthma.
NO is produced endogenously from the blood vessels and mucosa of the nose and paranasal sinuses. NO is naturally produced in youth and goes down with aging, mainly hampering the blood circulation to ear, brain, heart, and sex organs.
Humming increases the production of NO from sinuses and nasal mucosa. Eby explained humming as a sonic cleanser, cures the infection of sinuses. NO by decreasing the swelling of sinus ostia results into better drainage and oxygenation.[6] Humming exercise also increases the vital capacity. It is estimated that humming increases the endogenous generation of NO level by 15-fold as compared with the quite exhalation.[7] Because of its vasodilator effect, NO can control the filling of nasal capacitance vessels, thus nasal airflow, nasal mucosal temperature, and humidification, hence providing air conditioning to sinuses and respiratory passage. This, in turn, affects the ciliary flow and cleansing of the nose, paranasal sinuses, including nasopharyngeal tubes. Better air flow and ciliary clearances of nasopharyngeal tubes influence the ventilation and impedance of the middle ear resulting in an improvement in the quality of hearing. The NO generated during humming, by improving the Eustachian tube More Details function and ventilation of cochlea through the round window affects the cochlear physiology, neurotransmission, and regulation of cochlear blood flow.[8] It has been observed that adding a small amount of NO to the oxygen to the premature infants prevents blindness, cerebral palsy, and deafness.[9]
NO released by Bhramari accelerates the microcirculation of blood and Bhramari by vibration, declogs the tiny blood vessels of the brain and inner ear.
Bhramari Pranayama (Bee Breath)
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It is a breathing exercise; a humming sound is produced during exhalation with an effort to generate the echo in the ears. In modern medicine, higher frequency sound (ultrasound therapy) is a known modality in the treatment of tinnitus and sensorineural deafness. Apart from the restoration of hearing by stimulating the hair cells and generating action potential, Bhramari Pranayama is also quite effective in de-stressing.
The exercise can be performed sitting comfortably in calm place, eyes closed, relaxed mood with a smile on face, place your index finger gently in the ear canal or on tragal cartilage to gently block the ear canal. Take a deep breath and as you exhale slowly, make a loud continuous sustained pitch humming sound and generate an echo, focus your attention toward the inner ears. A high pitch sound gives better results. It also helps in regaining better speech recognition. It is an exercise of Hatha Yoga you have to imagine and give command through the brain that there is an increased circulation of oxygen and blood to the inner ear and your hearing is improving with every breath and echo of sound.[10]
Shanmukhi Mudra is a modification of Bhramari Pranayama for better and earlier improvement. The procedure is place your both thumbs at the inlet of external auditory canal, both hands' index fingers on the forehead just above the eyebrows at the level of Agya Chakra (solar plexus) middle fingers on the medial canthus of eyes, ring fingers on the ala of nose do not pinch or block the nasal airway, and little fingers on upper lip. Take a deep breath close your mouth with ballooning of cheek and tuck your chin into the chest, a high pitch continuous sustained humming sound is produced https://youtu.be/9rOnhM_WO6s.[11]
Diet influences your body, mind, and soul, hence you are what you eat, drink, and do (yoga).[5] Your life style changes, diet, correction of Vitamin D deficiency [12],[13] and yoga help you fight with disease. In diet, beetroot, spinach, lettuce, Chinese cabbage, radish, mustard leaf, carrots, and green beans are the sources for providing semi-essential amino acids which are precursor for the production of NO in the body. The production of NO is influenced and enhanced by exercise and humming sound.
Nitrite is converted into NO by the macrophages and endothelium of respiratory mucosa including mucosa of the nose and paranasal sinuses, which in turn dilates the vessel. The endothelium releases more NO on physical activity and in low cholesterol level. Stress reduces the release of NO. Horror movies reduce NO level, whereas comedy movies increase NO level.
Apart from calming the brain by improving the quality of sleep, NO helps memory and behavior by transmitting information between neurogenic cells in the brain, NO may increase the recognition of sense that is speech discrimination and improves the quality of hearing which goes down with the age.
Greeva Chalan (Cervical exercise) releases the muscular spasm, stiffness, and fixation of cervical spine bones leading to increase blood supply to the brain and inner ear; hence, cortical brain functioning will be better and improving the grasping power and speech discrimination. Skandh Chalan (Shoulder exercise) helps in overcoming upper girdle weakness and depression.
Materials and Methods
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In July 2015, publicity was done to make the public aware that institution is organizing a free deafness detection camp. Camp was attended by 72 patients of deafness. All the patients were screened thoroughly complete ENT examination; detailed history of deafness, tinnitus, and systemic disorders was taken. Blood pressure and blood sugar evaluation of all patients apart from pure tone audiometry and tympanometry were done.
A total of 15 middle-aged and senior citizens who did not benefit with the hearing aid were scrutinized who were having predominately sensorineural deafness, which were the subject for the present study.
The selection criteria
•Sensorineural deafness
•Willing to undergo yoga and follow-up yoga regularly for 3 months
•Residing in the vicinity of 3.0 km area of the hospital
•Not benefited with hearing aid.
Exclusion criteria
1.A clinical ear discharge or other systemic disease
2.Coronary heart disease.
Out of 15 patients, 2 patients lost follow-up in yoga after 2 months hence not included in the study.
Results
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Totally 13 patients were evaluated after 3 months of regular follow-up and practice maximum number of patients were between 55 and 60 years age group, that is, 6 (46.1%)[Table 1].
Table 1: Age and sex distribution
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All patients had sensorineural deafness only two patients had tinnitus and three patients had increased blood sugar (known diabetic).
All patients were evaluated after 3 months, two patients were satisfied whereas 11 patients had improvement of average 9 dB, two patients did not show improvement, out of which one was diabetic. Out of three known diabetic, one improved and blood sugar level came down to near normal limits. And also patient had hearing improvement [Table 2].
Table 2: Disease and improvement by yoga
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Two patients were of cervical spondylitis both improved. Out of 13 patients, 12 patients had overall betterment in the quality of life, one patient female 65 years who was not having any improvement in hearing, good yoga performer; although, audiometry showed 15 dB improvement, subjectively no improvement, she was enthusiastic to continue yoga.
All the five patients having a history of forgetfulness were subjectively better.
Snoring was notified in nine patients recovered significantly in all patients. One patient who had symptoms of benign prostate enlargement and increased prostate-specific antigen (PSA) claimed he is better and PSA came down.
Discussion
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No authentic published data could be searched of the Indian subcontinent to compare this preliminary pilot project. The study was conducted to evaluate the importance of yoga, lifestyle changes, diet modification and avoiding ototoxic drugs and chemicals in cases of sensorineural deafness. As discussed in material methods, the technique of yoga was collaborated with emphasis on breathing technique during cervical and shoulder exercise done to increase the vital capacity and better lung functioning.
Conclusion
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The preliminary pilot study shows that there is an improvement in hearing after 3 months in 11 (84.6%) and improvement in the quality of life 12 (92.3%). There was also improvement and control in diabetes or prostate symptoms. A preliminary study showing promising results and prompts further study which has been already initiated and we expect promising result in next few months.
References
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1.
World Health Organization. Deafness and Hearing Impairment Fact Sheet; 2014. Available from: http://www.who.int/mediacentre/factsheet/fs300/index. Back to cited text no. 1
2.
WHO. Global Estimates on Prevalence of Hearing Loss; 2012. Available from: http://www.who.int/pbd/deafness/WHO_GE_HL_pdf. Back to cited text no. 2
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Taneja MK. Deafness, a social stigma: Physician perspective. Indian J Otolaryngol Head Neck Surg 2014;66:353-8. Back to cited text no. 3
4.
Taneja MK, Quereshi S. Holistic approach to deafness. Indian J Otol 2015;21:1-3. Back to cited text no. 4
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Taneja MK, Varshney H, Taneja V, Varshney J. Ototoxicity, drugs, chemicals, mobile phones and deafness. Indian J Otol 2015;21:161-4. Back to cited text no. 5
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Harada N. Role of nitric oxide on purinergic signalling in the cochlea. Purinergic Signal 2010;6:211-20. Back to cited text no. 6
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Eby GA. Strong humming for one hour daily to terminate chronic rhinosinusitis in four days: A case report and hypothesis for action by stimulation of endogenous nasal nitric oxide production. Med Hypotheses 2006;66:851-4. Back to cited text no. 7
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Muñoz DJ, Thorne PR, Housley GD, Billett TE. Adenosine 5'-triphosphate (ATP) concentrations in the endolymph and perilymph of the guinea-pig cochlea. Hear Res 1995;90:119-25. Back to cited text no. 8
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Maniscalo M. Humming, nitric oxide and paranasal sinuses ventilation. Eur Respir J 2003;22:323-9. Back to cited text no. 9
10.
Taneja MK. Nitric oxide Bhramari Pranayam and deafness. Indian J Otol 2016;22:1-3. Available from: https://www.youtu.be/9rOnhM_WO6s. Back to cited text no. 10
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Taneja MK. Improving hearing performance through yoga. J Yoga Phys Ther 2015;5:194. Back to cited text no. 11
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Taneja MK. Role of Vitamin D in prevention of deafness. Indian J Otol 2012;18:55-7. Back to cited text no. 12
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Taneja MK, Taneja V. Vitamin D deficiency in E.N.T. Patients. Indian J Otolaryngol Head Neck Surg 2013;65:57-60. Back to cited text no. 13
... Eby explained humming as a sonic cleanser, cures the infection of sinuses by decreasing the swelling of sinus ostea resulting into better drainage and oxygenation. [3] Humming exercise also increases the vital capacity. It is estimated that humming increases the endogenous generation of nitric oxide level by 15-fold as compared with the quite exhalation. ...
... In support of this, a case report was described very recently 103 proposing that strong low pitch (130 Hz) humming was an effective means of treating chronic rhino-sinusitis (CRS). In this report a subject hummed frequently for 4 days in an attempt to treat the sinusitis. ...
... Concerning nasal NO, several studies have indicated that levels are increased in patients with rhinitis (29). However, others have shown no significant difference in nasal NO between patient with nasal symptoms and healthy individuals (30). ...
The prevalence of rhinitis is high and frequently observed in association with asthma. Although the persistence of predisposing factors such as rhinitis is frequently observed in adults, this has not yet been confirmed in children.
The aim of this present work is to show the relationship between rhinitis and asthma control in asthmatic children.
The authors carried out a cross-sectional study by collecting clinical, spirometric, and fractional exhaled nitric oxide (FeNO) data in children aged from 4 to 17 years.
One hundred seventeen children were included. Asthma control was optimal in 37.6%, suboptimal in 55.5% and poor in 7.3% of cases. A 74.3% of children were atopic and 62.5% had symptoms 34 of rhinitis. Rhinitis was more frequent when control of asthma was worse (p = .0001). Age (p = .002), asthma control (p < .001), atopy (p = .001), and presence of rhinitis (p = .012) were significantly associated with FeNO.
Our study confirms the strong relationship between upper airways and poor asthma control in the asthmatic child. Symptoms of rhinitis may be partly responsible for the increased fractional exhaled nitric oxide (FeNO) level, independently of the control of asthma. Evaluation of rhinitis should be included to improve assessment of asthma control in children.
... Therefore, 96 the search for nutrients that had anti-arrhythmic 97 activity was continued. 98 While experimenting with humming to induce 99 nasal nitric oxide (NO) production in the treatment 100 of chronic rhinosinusitis, it was observed that PACs 101 could be prevented simply by strong humming for 102 an hour on each of four consecutive days and there- 103 after as needed [6] ...
We searched for nutrient deficiencies that could cause cardiac arrhythmias [premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation, and related sinus pauses], and found literature support for deficiencies of taurine and l-arginine. Case histories of people with very frequent arrhythmias are presented showing 10-20g taurine per day reduced PACs by 50% and prevented all PVCs but did not prevent pauses. Adding 4-6g of l-arginine immediately terminated essentially all remaining pauses and PACs, maintaining normal cardiac rhythm with continued treatment. Effects of taurine useful in preventing arrhythmias include regulating potassium, calcium and sodium levels in the blood and tissues, regulating excitability of the myocardium, and protecting against free radicals damage. Taurine restored energy and endurance in one of the cases from a debilitated status to normal. Arrhythmias may also respond to taurine because it dampens activity of the sympathetic nervous system and dampens epinephrine release. l-arginine may have anti-arrhythmic properties resulting from its role as a nitric oxide (NO) precursor and from its ability to restore sinus rhythm spontaneously. Endogenous production of taurine and l-arginine may decline in aging perturbing cardiac rhythm, and these "conditional" essential nutrients therefore become "essential" and require supplementation to prevent morbidity and mortality. l-arginine is hypothesized to prevent cardiac arrhythmias by NO stabilization of the sinus node. Cardiac arrhythmias having no known cause in otherwise healthy people are hypothesized to be symptoms of deficiencies of taurine and arginine.
Objective
To review and assess the peer‐reviewed literature on the utility of mind‐body therapy (MBT) as an adjunct treatment in the management of otolaryngologic disease.
Data Sources
PubMed, Embase, and Cochrane.
Review Methods
Randomized control trials (RCTs) of MBTs in the management of otolaryngologic disease from 2002 to 2022 were identified and included according to predefined criteria. Interventions requiring expensive equipment were excluded because the goal of MBT is to be cost‐conscious. All studies were subjected to a two‐stage blinded screening, extraction, and appraisal process. The outcomes of the intervention and control groups were compared.
Conclusion
RCTs of MBTs, including breathing exercises (4), aromatherapy (2), biofeedback (2), meditation, (2), and yoga (2), have been studied in several otolaryngologic conditions, including septoplasty/rhinoplasty (3), head and neck cancer (2), facial palsy (2), and tinnitus (2). Most studies were of moderate risk of bias on appraisal, and each MBT studied was found to significantly reduce subjective and objective distress associated with the otolaryngologic condition in question.
Implications for Practice
Despite a paucity of strong evidence supporting the universal use of MBTs, our review suggests that MBTs are cost‐effective and easily deployable complementary tools in the management of otolaryngologic disease. Future large, methodologically rigorous RCTs are needed to address the limitations of the included studies, such as improper blinding and inappropriate statistical analysis. As MBTs are studied further, a case for their current use can be made because of their low cost and minimal risk to patients.
A natural heme deficiency that exists in cells outside of the circulation broadly compromises the heme contents and functions of heme proteins in cells and tissues. Recently, we found that the signaling molecule, nitric oxide (NO), can trigger or repress the deployment of intracellular heme in a concentration-dependent hormetic manner. This uncovers a new role for NO and sets the stage for it to shape numerous biological processes by controlling heme deployment and consequent heme protein functions in biology.
The upper and lower respiratory airways interact in many ways. Important, well-known nasal functions include the filtering, warming, and humidification of inspired air before inhalation into the lungs. Nasal breathing aids oxygen absorption and facilitates carbon dioxide excretion. Nasal mucosal inflammation results in lower airway inflammation, and vice versa. A subsequent systemic inflammatory response amplifies the response to inflammatory stimuli in other areas of the respiratory airway. Inflammatory mediators and/or infectious pathogens may also be transported along the respiratory mucosa or through the airways. Neuronal responses may play a role, although the existence of nasobronchial reflexes remains controversial. Nitric oxide and carbon dioxide may act as aerocrine messengers. Patients with asthma, bronchiectasis, and chronic obstructive pulmonary disease frequently have upper respiratory tract disease and vice-versa. Epidemiological, physiological, and clinical evidence support a “unified airway” model.
The traditional Indian healthcare system of Yoga contains a wealth of health-promotional practices-some of which are based on "humming." "Humming" is produced when a wordless sound is forced to exit through the nose while keeping the mouth either fully closed or nearly closed; it is a low, prolonged, and buzzing sound. In humming practices like "Bhramari pranayama" (normal inhalation followed by lengthened exhalation + bee-like humming), there is a full-mouth closure,1 and in practices like "OM chanting" (normal inhalation followed by lengthened exhalation +OM humming), there is a near-closure. Besides these, other mantra-oriented practices also generate a similar humming effect.
In this article, the binding abilities of arginine, citrulline, N-acetyl citrulline and thiocitrulline on the active sites of SARS-COV-2 protease have been investigated using in-silico studies. All the above ligands bind selectively and preferentially to Cys-145 active site and also to other amino acids surrounding to it in the main protease. Of which arginine forms less number of weaker bonds compared to the other ligands, it by itself is a precursor for the formation of citrulline analogues with in the cell. Major advantage of using the above ligands is that in addition to its preferential binding, they have the ability to increase the immunity by assisting NO generation. Our results show that N-acetyl citrulline, citrulline, thiocitrulline and arginine may be used as a supplement during the treatment of SARS-COV-2.
Albert Einstein was one of the greatest physicists in recent history and his contributions changed the paradigm of science in the 20th century. From this, it was proposed the understanding that all matter is energy, and we can assume the understanding that the human body is a dynamic energy system. Energy and matter are two different manifestations of the same universal substance from which we are all formed, atoms. It is known that the movement between the constituent parts of the atom (electrons, neutrons, protons and smaller particles) and the forces that connect them, generates energy. Since the atoms are in constant movement, what can be measured is vibration. Therefore, in this chapter, we propose to present some millenary therapies like acupuncture, yoga, apitherapy and, more recently, Homeopathy, under the point of view of vibrational integrative therapies, exploring the hypothesis that through these therapies we can adapt the waves generated in the bodies to transform them into personalized therapeutic agents.
The Advanced Centre for Yoga Therapy Education and Research (ACYTER), a collaborative venture between JIPMER, Puducherry and Morarji Desai National Institute of Yoga (MDNIY), New Delhi was established by an MOU between JIPMER and MDNIY in June 2008 and focussed primarily on the role of Yoga in the prevention and management of cardiovascular disorders (CVD) and diabetes mellitus (DM). More than 30,000 patients benefited from Yoga therapy consultation and attended therapy individual and group sessionsWith the active collaboration of MDNIY, New Delhi many research projects were conducted at JIPMER as collaborative efforts between ACYTER and the Departments of Physiology, Medicine, Biochemistry and Cardiology.
Slow, deep, pranayama-based breathing training has been shown to be effective in reducing blood pressure (BP). The present study was undertaken to determine immediate effects of performing pranava pranayama on cardiovascular parameters in hypertensive patients. 29 hypertensive patients who were on medical treatment and also attending yoga sessions were recruited for the present study. Supine heart rate (HR) and BP were recorded before and after performance of pranava pranayama for five minutes. Post intervention statistical analysis revealed a significant (P < 0.05) reduction in systolic pressure (SP) and a more significant (P < 0.01) reduction in HR, pulse pressure and double product (Do P). The reduction in rate-pressure product (RPP) was highly significant (P < 0.001). Pranava pranayama is effective in reducing HR and SP in hypertensive patients within five minutes of the practice. This may be due to a normalization of autonomic cardiovascular rhythms as a result of increased vagal modulation and/or decreased sympathetic activity and improved baroreflex sensitivity along with an augmentation of endogenous nitric oxide production. Our findings have potential therapeutic applications in day-to-day as well as clinical situations where blood pressure needs to be brought down at the earliest. The significant fall in RPP and Do P signifies a reduction in oxygen consumption and work done by the heart. It is concluded that pranava pranayama, a simple and cost effective technique can be used in the management of hypertensive patients in addition to the regular medical management. Further studies are required to enable a deeper understanding of the mechanisms involved and its usefulness in the long- term management of hypertension.
Complementary and alternative medicine encompasses a wide range of practices. Eisenberg et al. defined this practice as "medical interventions not taught widely at U.S. medical schools or generally available at U.S. hospitals" [1]. Recently, a great interest has developed for the practice of complementary and alternative medicine (CAM), as evidenced by the number of publications on this subject. In 1999, the National Institutes of Health (NIH) established the National Center for Complementary and Alternative Medicine (NCCAM), which is funding research in this area. This is a further indication that "Western Medicine" is embracing certain aspects of the alternative practices and attempting to glean knowledge from these long-practiced remedies. Unfortunately, for practitioners in the U.S. many of the studies evaluating the efficacy of CAM have been published in languages other than English. In 1990, a survey reported that one third of the population of the United States used some form of CAM, and of those, nearly three-quarters did not inform their physicians of such practice [1]. In a subsequent study focusing on the changes in patients' practices between 1990 and 1997, the authors demonstrated that the use of CAM increased from 33.8% to 42.1%. Expenditure on CAM and CAM-related products was estimated to be $13.7 billion in 1990 and increased to approximately $21.2 billion in 1997 [2]. Moreover, this study estimated that the number of visits to practitioners of complementary medicine exceeded that of the number of visits to primary care physicians. The use of CAM in otorhinolaryngology permeates all the discipline's subspecialties, and thus the American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) has established a Committee on Alternative Medicine to serve as a resource for information on this practice. The most common forms of CAM employed are herbal medicines, acupuncture, homeopathy, massage, mind-body medicine, and chiropractic manipulation [3]. In most of these arenas there is no evidence of safety or efficacy. In rhinology, there are several conditions for which CAM has been widely used, including the common cold/upper respiratory infections, allergic rhinitis, acute rhinosinusitis (ARS), and chronic rhinosinusitis (CRS). In 2001, a survey of 175 patients with rhinosinusitis in Northern California reported that 43% of patients used some form of CAM to alleviate their symptoms, with herbal medicine being utilized by 26% of subjects [4]. Krouse et al. in 1999 reported on the use of CAM by 120 patients and found that 35% of the cohort underwent chiropractic treatment, 29% herbal medicines, and 19% acupuncture for the treatment of their sinus conditions [5]. Thus, clinicians must be aware of these practices and actively query their patients on the use of CAM, not only for their potential benefits, but because they may have potential adverse effects, interact with traditional therapies, or complicate surgical intervention. © 2008 Springer Science+Business Media, LLC. All rights reserved.
The worldwide interest in the use of complementary and alternative medicine (CAM) has been established in multiple surveys. Chronic rhinosinusitis (CRS) is often an unremitting disease with frequent troubling relapses, and despite wide use of endoscopic sinus surgery, conventional medicine may have a smaller contribution than expected. Because of prevalent use of CAM among patients, it is important that physicians acquire basic knowledge of this subject. We studied the prevalence of CAM use among CRS patients in Israel.
Use of CAM was evaluated in a cohort of consecutive adult patients with CRS.
An outpatient clinic in a tertiary medical centre.
Patients were asked to fill out an anonymous questionnaire containing demographic data and data pertaining to allergy, traditional medical and surgical treatment use of CAM, and modalities used.
Ninety patients were included. Nineteen of them (21%) reported CAM use. This included herbal medicine, vitamins, homeopathy, acupuncture, massage, reflexology, yoga, and chiropractics. There was a tendency, although not statistically significant, for patients with allergy and a history of sinus surgery to use CAM.
The prevalence of CAM use among patients with CRS in Israel is high and may correlate with the presence of allergies and a history of sinus surgery.
In the rescue treatment of acute asthma, injected and inhalant magnesium are relatively weak having demonstrated value only in severe illness, although theoretical and laboratory considerations suggest that magnesium should be strongly effective as an asthma rescue agent. It was hypothesized that a mouth-lung biologically closed electric circuit (BCEC) exists capable of nearly instantly transporting positively charged magnesium ions from the mouth and throat into the lungs. One hundred milligram magnesium (magnesium chloride) 4-g throat lozenges producing 100+ mM magnesium ion concentration in saliva were tested to determine if they had beneficial effects in asthma rescue and prevention. Subjects were selected based solely on need for asthma rescue, and lozenges were used as needed. Case histories are presented showing the nearly immediate effect of magnesium chloride throat lozenges in terminating and preventing asthma attacks. Throat lozenges containing magnesium chloride produced much more rapid and stronger benefits than has been reported for inhaled and injected magnesium. An added benefit from magnesium chloride lozenge treatment of asthma was relaxation. In this first report of its kind, magnesium chloride throat lozenges appeared to provide rescue benefits in the treatment of asthma equivalent to pharmaceutical asthma drugs. Countering these benefits, strong ionic magnesium solutions greatly increase rhinovirus, herpesvirus and Candida albicans in vitro, and appear to worsen these infections in humans. Magnesium lozenges releasing concentrated magnesium ions appear contraindicated during common colds, oral herpes infections, chronic rhinosinusitis, oral and respiratory infections in general, and their use must immediately be terminated if respiratory or oral symptoms worsen. Double-blind, placebo-controlled, clinical trials in people without respiratory or oral infections are needed to determine magnesium lozenge safety, and the extent by which drug treatment of asthma can be reduced.
This review briefly explains the basic facts about nitric oxide, which is entering clinical practice as a measure of lower airways inflammation and is likely also to be employed in otorhinolaryngological practice.
These include the validity of nasal nitric oxide in diagnosing primary ciliary dyskinesia and in monitoring the response to chronic rhinosinusitis therapy. The nasal nitric oxide value combined with a humming manoeuvre, which increases the passage of nitric oxide from the sinuses to the nose if the ostiomeatal complex is patent, could reduce the need for computed tomography scans. The link between nitric oxide production and ciliary beating requires further exploration. Therapeutic adjustments to nitric oxide production are under investigation.
Nitric oxide is likely to prove highly relevant to airways defence, as well as being an inflammatory mediator. Nasal nitric oxide probably explains some of the benefit of nasal rather than mouth breathing.
A new collection of ideas from Medical Hypotheses by Roger Dobson is entitled Death can be cured and 99 other Medical Hypotheses. It consists of humorous summaries of Medical Hypotheses articles from the past 30 years. The book's humour derives mainly from the subject matter, although sometimes also from the 'unconventional' approach of the authors with respect to matters such as evidence, argument or inference. Medical Hypotheses has generated such a lot of apparently- or actually-bizarre ideas because it aims to be open to potentially revolutionary science. The journal's official stance is that more harm is done by a failure to publish one idea that might have been true, than by publishing a dozen ideas that turn out to be false. Bizarre ideas tend to catch attention, and may stimulate a valuable response--even when a paper is mostly-wrong. A paper may be flawed but still contain the germ of an idea that can be elaborated and developed. The journal review process is susceptible to both false positives and false negatives. False positives occur when we publish an idea that is wrong; false negatives occur when we fail to publish an important idea that is right, and a potential scientific breakthrough never happens. False positives are more obvious, since the paper will be ignored, refuted, or fail to be replicated--and often attracts criticism and controversy. Editors may therefore take the more cautious path of avoiding false positives more assiduously than false negatives; however, this policy progressively favours less-ambitious science. Consequently, in Medical Hypotheses the 'set point' of risk is nearer to the false positive end of the spectrum than for most journals - and the publication of many apparently-bizarre papers is a natural consequence of this policy.
Air pollution episodes have been associated with increased cardiovascular hospital admissions and mortality in time-series studies. We tested the hypothesis that patients with implanted cardioverter defibrillators experience potentially life-threatening arrhythmias after such air pollution episodes. We compared defibrillator discharge interventions among 100 patients with such devices in eastern Massachusetts, according to variations in concentrations of particulate matter, black carbon, and gaseous air pollutants that were measured daily for the years 1995 through 1997. A 26-ppb increase in nitrogen dioxide was associated with increased defibrillator interventions 2 days later (odds ratio = 1.8; 95% confidence interval = 1.1-2.9). Patients with ten or more interventions experienced increased arrhythmias in association with nitrogen dioxide, carbon monoxide, black carbon, and fine particle mass. These results suggest that elevated levels air pollutants are associated with potentially life-threatening arrhythmia leading to therapeutic interventions by an implanted cardioverter defibrillator.
To reevaluate the current criteria for diagnosing allergic fungal sinusitis (AFS) and determine the incidence of AFS in patients with chronic rhinosinusitis (CRS).
This prospective study evaluated the incidence of AFS in 210 consecutive patients with CRS with or without polyposis, of whom 101 were treated surgically. Collecting and culturing fungi from nasal mucus require special handling, and novel methods are described. Surgical specimen handling emphasizes histologic examination to visualize fungi and eosinophils in the mucin. The value of allergy testing in the diagnosis of AFS is examined.
Fungal cultures of nasal secretions were positive in 202 (96%) of 210 consecutive CRS patients. Allergic mucin was found in 97 (96%) of 101 consecutive surgical cases of CRS. Allergic fungal sinusitis was diagnosed in 94 (93%) of 101 consecutive surgical cases with CRS, based on histopathologic findings and culture results. Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of AFS patients.
The data presented indicate that the diagnostic criteria for AFS are present in the majority of patients with CRS with or without polyposis. Since the presence of eosinophils in the allergic mucin, and not a type I hypersensitivity, is likely the common denominator in the pathophysiology of AFS, we propose a change in terminology from AFS to eosinophilic fungal rhinosinusitis.
The susceptibility of Candida albicans to several fatty acids and their 1-monoglycerides was tested with a short inactivation time, and ultrathin sections were
studied by transmission electron microscopy (TEM) after treatment with capric acid. The results show that capric acid, a 10-carbon
saturated fatty acid, causes the fastest and most effective killing of all three strains of C. albicans tested, leaving the cytoplasm disorganized and shrunken because of a disrupted or disintegrated plasma membrane. Lauric acid,
a 12-carbon saturated fatty acid, was the most active at lower concentrations and after a longer incubation time.
Nasal nitric oxide (NO) levels increase greatly during humming compared to silent exhalation. In this study, the physiological and anatomical factors that regulate NO release during humming have been characterised in 10 healthy subjects and in a model of the sinus and the nose. Single-breath humming caused a large initial peak in nasal NO output, followed by a progressive decline. The NO peak decreased in a step-wise manner during repeated consecutive humming manoeuvres but recovered completely after a silent period of 3 min. Topical nasal application of an NO synthase inhibitor reduced nasal NO by >50% but had no effect on the increase evoked by humming. Silently exhaled nasal NO measured immediately after repeated humming manoeuvres was between 5-50% lower than basal silent NO exhalation, suggesting variable continuous contribution from the sinuses to nasal NO. Among the factors known to influence normal sinus ventilation, ostium size was the most critical during humming, but humming frequency was also of importance. In conclusion, humming results in a large increase in nasal nitric oxide, which is caused by a rapid gas exchange in the paranasal sinuses. Combined nasal nitric oxide measurement with and without humming could be of use to estimate sinus ventilation and to better separate nasal mucosal nitric oxide output from sinus nitric oxide in health and disease.
Common colds were shortened by 7 days in a 1984 clinical trial using zinc gluconate throat lozenges each 2 h. Between then and 2004, 10 other double-blind, placebo-controlled clinical trials showed widely varying results. This re-analysis of these trials presents solution chemistry methods to elucidate differences in efficacy. Statistically significant correlation was shown between total daily dosages of positively charged zinc species and reductions in median (p = 0.005) and mean duration (p < 0.02) of common colds in these trials.
Animal models suggest that the cardiovascular effects of air pollution result in part from inflammation caused by proinflammatory mediators originating in the lung. In a human study of the cardiovascular effects of air pollution, we aimed to evaluate the potential association between air pollution levels and the fraction of exhaled nitric oxide (FE(NO)), a non-invasive measure of airway inflammation.
Breath samples were collected weekly between September and December 2000 in a community based group of elderly subjects (median age 70.7 years) in Steubenville, Ohio. The samples were analysed for NO. Air pollution levels were measured concurrently at a central site monitor.
An increase in the 24 hour average PM(2.5) concentration of 17.7 micro g/m(3) was associated with an increase in FE(NO) of 1.45 ppb (95% CI 0.33 to 2.57) in models adjusted for subject, week of study, day of the week, hour of the day, ambient barometric pressure, temperature, and relative humidity. This represents a change of approximately 15% compared with the mean FE(NO) in the cohort (9.9 ppb). A significant association was also observed for a 24 hour moving average of ambient NO (0.83 ppb increase, 95% CI 0.26 to 1.40). In two-pollutant models, the magnitude and precision of the PM(2.5) effect was not reduced and the ambient NO effect was no longer significant. The associations between FE(NO) and PM(2.5) were significantly higher in subjects with a doctor's diagnosis of COPD (p value for interaction = 0.03).
Ambient pollution may lead to airway inflammation as measured by FE(NO). These subclinical inflammatory changes may be an important step in the pathogenesis of the cardiopulmonary effects induced by exposure to air pollution.
Nitric oxide (NO) inhibits vascular inflammation, but the molecular basis for its anti-inflammatory properties is unknown. We show that NO inhibits exocytosis of Weibel-Palade bodies, endothelial granules that mediate vascular inflammation and thrombosis, by regulating the activity of N-ethylmaleimide-sensitive factor (NSF). NO inhibits NSF disassembly of soluble NSF attachment protein receptor (SNARE) complexes by nitrosylating critical cysteine residues of NSF. NO may regulate exocytosis in a variety of physiological processes, including vascular inflammation, neurotransmission, thrombosis, and cytotoxic T lymphocyte cell killing.
The effects of taurine on the electrical activity of the heart were studied in isolated preparations from guinea pigs and in situ hearts of dogs that were administered toxic doses of strophantin K. In the 1st min after exposure of isolated hearts to taurine (0.05 mg/mv or more), the height of the T wave increased, the S T interval lengthened, and bradycardia ensued. At high taurine concentrations (10 mg/ml), inversion of the T wave and downward displacement of the S T segment were observed. Taurine restored abnormal electrocardiograms (ECGs) to normal, including S T segment abnormalities, T wave inversions, and disorders of conduction. On the other hand, taurine aggravated the ECG abnormalities seen in hearts perfused with K + free buffer, but sustained electrical activity if added early in the period of potassium deficiency. Taurine uptake by the isolated heart was estimated by disappearance from the medium and was found to be intensified by K + depletion. In dogs given toxic doses of strophanthin K, taurine reversed the ECG abnormalities in the initial 40 to 50 min, after which the abnormalities reappeared. If toxic effects were not present, taurine exerted an inotropic effect. These findings indicate that taurine is able to regulate the excitability of the myocardium, possibly by modifying membrane permeability to potassium. It is suggested that this effect involves penetration of taurine into the cell and its conversion to isethionic acid.
Goblet cells are situated in the epithelium of the conducting airways, often with their apical surfaces protruding into the lumen, a location which fits them for a rapid response to inhaled airway insults. Together with the submucosal glands, goblet cells secrete high molecular weight mucus glycoproteins (mucins), which confer upon the airway surface fluid the requisite biochemical and biophysical properties which determine the efficiency of entrapment and transportation of inhaled irritants, particles and micro-organisms. The diversity of glycosylation of airway mucins may be important in facilitating adherence of micro-organisms to mucus prior to mucociliary clearance. Other secretory products, including lipids and "small" glycoproteins, may also be produced by goblet cells. It is possible that goblet cells have the potential to produce markedly more mucus than do the glands. Mucins are tightly packed in the intracellular granules of the goblet cell. The morphology of these granules varies with fixation technique, and release of mucins may be via a combination of merocrine and apocrine secretion. Discharge of mucus is accomplished remarkably rapidly (tens of milliseconds) and vast quantities of mucus are released (size expansions from the granule of many hundredfold). Depending upon species and preparation, goblet cells discharge mucus in response to a wide variety of stimuli, including proteinases, irritant gases, inflammatory mediators, reactive oxygen species, nerve activation and changes in the biophysical environment. Under normal conditions, goblet cell proliferation and differentiation, particularly to ciliated cells, contributes to maintenance of the airway epithelial cell population. In addition to participating in acute airway defence, goblet cells increase in number in response to chronic airway insult, with a resultant increase in output of mucus. The increase in number of cells is via hyperplastic and metaplastic mechanisms. Early triggers for the development of a hypersecretory epithelium include excessive discharge of mucus and increased expression of airway mucin messenger ribonucleic acid (mRNA). Cessation of chronic airway stress rapidly reverses the increased number of goblet cells. Irritant-induced increases in number of goblet cells can be inhibited by a variety of drugs with anti-inflammatory and mucoregulatory properties, and the reversal to normal numbers after cessation of the irritation is speeded by these drugs. The ability of goblet cells to be progenitors of ciliated cells, to rapidly produce vast quantities of mucus in response to acute airway insult, and to change in number according to variations in chronic insult indicates that these cells are vitally important responsive and adaptable front-line defenders of the airways.
Right ventricular failure following cardiac transplantation is most commonly related to pre-existent recipient pulmonary hypertension secondary to chronic congestive heart failure. Although nitric oxide has had some role clinically in improving pulmonary hemodynamics and right ventricular function in this setting, an appropriate large-animal model of stable pulmonary hypertension has not been available for basic investigation of this problem. This study was designed to examine the hemodynamic and inotropic effects of inhaled nitric oxide using a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. Eight mongrel dogs (22-25 kg) were used. All animals underwent percutaneous pulmonary artery catheterization to measure right heart hemodynamics prior to and 8 weeks after a right atrial injection of monocrotaline pyrrole. Eight weeks post-injection, all hearts were instrumented with a pulmonary artery flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and following nitric oxide administration. Eight weeks post-monocrotaline pyrrole injection, significant increases were observed in the pulmonary hemodynamics compared to pre-injection. Nitric oxide led to significant decreases in pulmonary vascular impedance. Significant improvements in pulmonary blood flow, transpulmonary efficiency, and right ventricular contractility were also observed. This investigation demonstrates the well-known clinical effects of nitric oxide in improving pulmonary hemodynamics which were also associated with an increase in pulmonary blood flow, transpulmonary efficiency, and right ventricular contractility in the setting of monocrotaline pyrrole-induced pulmonary hypertension.
The paranasal sinuses are major producers of nitric oxide (NO). We hypothesized that oscillating airflow produced by humming would enhance sinus ventilation and thereby increase nasal NO levels. Ten healthy subjects took part in the study. Nasal NO was measured with a chemiluminescence technique during humming and quiet single-breath exhalations at a fixed flow rate. NO increased 15-fold during humming compared with quiet exhalation. In a two-compartment model of the nose and sinus, oscillating airflow caused a dramatic increase in gas exchange between the cavities. Obstruction of the sinus ostium is a central event in the pathogenesis of sinusitis. Nasal NO measurements during humming may be a useful noninvasive test of sinus NO production and ostial patency. In addition, any therapeutic effects of the improved sinus ventilation caused by humming should be investigated.
Chronic rhinosinusitis (CRS) is the most common chronic disease that is frequently refractory to treatment.
We sought to establish the safety and demonstrate the clinical efficacy of intranasal antifungal drug therapy in patients with CRS in a pilot trial.
A prospective open-label trial used amphotericin B as a medical treatment in 51 randomly selected patients with CRS. The antifungal agent was applied intranasally as 20 mL of a 100 microg/mL solution twice daily. The outcome was measured by using their symptoms and by using an endoscopic scoring system in all patients. In addition, pretreatment and posttreatment coronal computed tomographic scans of the nose and sinuses were available for evaluation in 13 patients.
By using amphotericin B, improvement of sinusitis symptoms was observed in 38 (75%) of 51 patients. Endoscopically, 18 (35%) of 51 patients became disease free, and an additional 20 (39%) of 51 had improvement of at least one stage (P <.001). No effect was seen in 13 (25%) of 51 patients. The available computed tomographic scans before and after treatment demonstrated a significant reduction in the inflammatory mucosa thickening that had occluded the paranasal sinuses (P <.0001 in maxillary sinus).
This open-label pilot trial demonstrates that direct mucoadministration of an antifungal drug appears to be both safe and effective in the treatment of patients with CRS. Therefore controlled and blinded trials are indicated to clarify the novel role of intranasal antifungal drugs in the treatment of CRS.
Cardiac parasympathetic activity reduces susceptibility to potentially lethal ventricular arrhythmias in heart failure and ischemic heart disease. This influence is mediated in large part by antagonism of the adverse cardiac effects of sympathetic overactivity ("indirect" parasympathetic activity) in addition to the "direct" effects of muscarinic stimulation. Nitric oxide modulates parasympathetic cardiac signaling in some animal models, but human data are lacking. We have investigated the influence of endogenous nitric oxide on cardiac responses to parasympathetic stimulation in healthy humans. In 18 volunteers, we studied chronotropic and inotropic responses to muscarinic stimulation, both before and after prestimulation with isoproterenol. Cardiac muscarinic stimulation was achieved using an intravenous bolus of the short-acting cholinesterase inhibitor, edrophonium. Responses were assessed during a background infusion of a nitric oxide synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA]), placebo (saline), or phenylephrine (vasoconstrictor control) in a single-blind, random order, crossover protocol. L-NMMA did not affect chronotropic responses to edrophonium alone (direct parasympathetic activity). The decrease in heart rate attributable to "indirect" parasympathetic activity (derived by comparison with the effect of edrophonium during concurrent adrenergic stimulation) was substantially attenuated by L-NMMA in comparison to both control infusions. No modification of muscarinic inotropic responses by L-NMMA was apparent in comparison to the vasoconstrictor control. Nitric oxide exerts a powerful facilitating influence on indirect (antiadrenergic) but not direct human cardiac parasympathetic control. Stimulation of the endogenous nitric oxide pathway might enhance parasympathetic protection against the adverse influences of cardiac sympathetic overactivity.
The common cold is a clinical syndrome triggered by a variety of viral pathogens, but rhinoviruses are the most frequent cause. Complications of such infections include sinusitis, otitis media, and exacerbations of asthma and chronic obstructive lung disease. There is growing interest in host innate defence responses that may regulate the severity of viral responses. We will review recent evidence that nitric oxide is an important contributor to the host response during colds.
Infection of human airway epithelial cells with human rhinovirus has been shown to lead to the increased expression of inducible nitric oxide synthase both in vitro and in vivo. This increase in epithelial inducible nitric oxide synthase correlates with increased levels of nitric oxide in exhaled air. Importantly, nitric oxide can inhibit human rhinovirus-induced epithelial expression of several pro-inflammatory cytokines and can inhibit viral replication in epithelial cells in vitro. Moreover, nitric oxide can modulate several signal transduction pathways that are associated with cytokine generation. Nitric oxide can also nitrosylate viral proteases and can interact with the immune system. Consistent with these observations, pilot studies have indicated that the increased generation of nitric oxide during rhinovirus infections is associated with fewer symptoms and more rapid viral clearance.
Further studies are warranted to evaluate the role of nitric oxide in colds and to determine whether the administration of nitric oxide donor compounds could be a viable therapeutic approach for viral exacerbations of airway diseases.
Ponikau used a novel collection and culturing method to recover fungi from nasal secretion in patients with chronic rhinosinusitis. The same method had been used previously in Europe with a similar result. However, the use of Ponikau's method has not been reported in Asia.
Fifty-one patients with chronic rhinosinusitis who were scheduled for functional endoscopic sinus surgery were enrolled in this study. One day before functional endoscopic sinus surgery, swab specimens were obtained from middle meatuses and were sent to the microbiology laboratory for routine bacterial and fungal cultures. Then, the same nasal cavity was lavaged with 20 mL of sterile water. The exhaled fluid was collected and processed using the Ponikau method. Skin testing with Candida extract was done also in all patients. The results obtained by different culture methods were compared.
Bacteria grew from 45 of 51 swab specimens. The culture rate was 88.2%. Fungi were cultured from 6 of 51 swab specimens (11.8%) and from 25 of 51 lavage specimens (49%). The fungal culture rates were significantly different between swab and lavage specimens (p < 0.001). Candida was the most common cultured fungi in the lavaged specimens.
The study showed that Ponikau's method resulted in a higher fungal culture rate than that obtained with the swab method, but the culture rate was lower than the bacterial culture rate. Additional study is needed to investigate the role of fungi in the pathogenesis of chronic rhinosinusitis.
The presence of bacterial colonization in non-healing wounds and burn injuries interferes significantly with the normal process of healing. Recent evidence suggests that nitric oxide (NO) plays an important role in host defense against infection and regulates wound healing and angiogenesis. We investigated the potential application of a medical-grade gaseous form of NO (gNO) as a novel antibacterial agent in wound infection. Using a continuous horizontal-flow delivery system, the antibacterial activity of gNO was tested in vitro against a range of pathogens, including clinical isolates of Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Group B Streptococcus, Pseudomonas aeruginosa, and Candida albicans. To probe the effect of topical application of gNO on the human skin, the proliferation and extracellular matrix gene expression of human dermal fibroblasts in culture were also analyzed by (3)H-thymidine incorporation assay and Northern blot techniques, respectively. Potent bacteriocidal activity was observed at 200 ppm gNO with an average of 4.1 +/- 1.1 h to completely stop bacterial growth. Interestingly, this dose of gNO did not show any cytotoxic effect in human dermal fibroblasts in culture exposed for up to 48 h. Analysis of gene transcription in fibroblasts revealed a significant increase in MMP-1 mRNA expression as early as 2 h post-exposure to gNO. Although to a lesser degree, a significant reduction in type I procollagen was also observed in the same fibroblasts. The results of this study suggest that exogenous gaseous NO has potent significant antibacterial properties that can be beneficial in reducing bacterial burden in infected wound in burn injuries or non-healing ulcers.
Nitric oxide (NO) is thought to reduce blood pressure by evoking vasodilation either directly by causing relaxation of vascular smooth muscle or indirectly by acting in the rostral brainstem to reduce central sympathetic outflow, which decreases the release of norepinephrine from sympathetic nerve terminals. An increasingly large body of literature suggests that alterations in the NO system may play an important role in the development or maintenance of clinical hypertension. As proof of concept, pharmacological inhibition of nitric oxide synthase (NOS) in humans and animals causes moderate to severe hypertension. Certain forms of secondary hypertension are accompanied by the accumulation of endogenous NOS inhibitors, which may contribute to the development of hypertension. Furthermore, targeted disruption of the endothelial isoform of NOS in mice causes moderate hypertension, implying that hypertension may also develop from reductions in NOS expression. These gene knockout studies in animals have initiated the search for single nucleotide polymorphisms in human NOS genes, which could potentially lead to decreases in NOS protein expression. Conversely, increases in NOS expression or NO production have been linked with several commonly used cardiovascular therapies, including exercise training and the use of both statins and angiotensin-converting enzyme inhibitors. Finally, increases in the production of oxidants such as superoxide anion can lead to the inactivation of NO, thereby reducing NO bioavailability. Thus, alterations in the expression or activity of NOS or in the availability of NO have the potential to play a causal role in clinical hypertension. The purpose of this article is to show how emerging basic research on the NO pathway is elucidating novel antihypertensive drug targets that are on the cusp of clinical application.