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How do we elucidate the mechanism behind nasal irrigation (Jalneti) leading to relief from allergies and respiratory infections?

Image credit: Photo by Andrea Piacquadio from Pexels

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Shubhankar Kulkarni
Shubhankar Kulkarni Mar 02, 2021
Nasal irrigation (Jalneti) has been practiced for ages. Its use has been indicated in the prevention of upper respiratory disorders and recently, COVID-19. What is the molecular mechanism behind the modulation of our immune system?

Here is how nasal irrigation is performed. This is a passive process where you create a slope for the water to flow. For kids, an active process is used where water is pushed in their nose using a syringe (another example). Although the effects of nasal irrigation on the mitigation of allergic symptoms like rhinorrhea, sneezing, nasal congestion, etc. have been reported, the underlying molecular mechanisms have not been studied in much detail. It is suggested that nasal irrigation performs a cleansing action and removes the pollen and other allergens, thus, leading to a reduced allergic reaction. A study used nasal irrigation as a non-invasive way of detection of the coronavirus, which is in line with the cleansing effect of the therapy.

However, another recent study has indicated a preventive action of nasal irrigation from COVID-19 infection. Would simple cleansing work as prevention against the coronavirus? It has been suggested that contact with water and the solutes therein elicits the secretion of mucus and maintenance of optimum humidity on the mucosal epithelium. Also, a regular practice of nasal irrigation builds the mucosal renewal rate (the cleansing effect). Here is some more information on the topic.

  1. What experiments can be performed to confirm this/ elucidate other possible mechanisms using modern science?
  2. Do you perform nasal irrigation? What are your thoughts/ hypotheses on how it might work?
  3. Are other immune cells like macrophages involved in the process? I am not suggesting that it is an adaptive response. Maybe nasal irrigation boosts native immunity. Maybe it improves immune surveillance. What do you think?

[1]Singh S, Sharma N, Singh U, Singh T, Mangal DK, Singh V. Nasopharyngeal wash in preventing and treating upper respiratory tract infections: Could it prevent COVID-19? Lung India. 2020 May-Jun;37(3):246-251. doi: 10.4103/lungindia.lungindia_241_20. PMID: 32367847; PMCID: PMC7353928.

[2]Gelardi M, Taliente S, Piccininni K, Silvestre G, Quaranta N, Ciprandi G. Nasal irrigation with Nasir® in children: a preliminary experience on nasal cytology. J Biol Regul Homeost Agents. 2016 Oct-Dec;30(4):1125-1130. PMID: 28078863.

[3]Gupta A, Gupta B. Jal Neti Sample for COVID Detection: A Novel Hypothesis. Indian J Otolaryngol Head Neck Surg. 2020 Aug 27;73(1):1-3. doi: 10.1007/s12070-020-02081-8. Epub ahead of print. PMID: 32868993; PMCID: PMC7450481.

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Creative contributions

Can antimicrobial properties of NaCl play the main role?

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Povilas S
Povilas S Mar 09, 2021
Dissolving salt in the water you rinse your nostrils with not only eliminates the irritation of the nasal lining but also possibly kills some of the microorganisms present in the nostrils. This would depend on the concentration of the salt solution and the types of microorganisms that come in contact with it and their susceptibility level. When it comes to COVID-19, there seems to be a debate about whether this practice can have any positive effect. What about other microorganisms that cause respiratory infections, like rhinitis? Many bacteria are involved. Bacteria seem to be more susceptible to NaCl than viruses. Can salt solution have any substantial effect when it comes to killing microorganisms directly inside the nasal passages?

I do rinse my nose and throat with salt solution regularly. I don't do it the original Jala Neti way as shown in the video, but rather by inhaling salty water into the nostrils and then blowing and spitting it out. I used to do it before covid, but rather rarely, more in the presence of rhinitis, cold, etc. Now I do it regularly, mostly after coming back home from outside. I believe that when done regularly it helps prevent respiratory infections, but this is a hunch reasoning, it's hard to evaluate it objectively.
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Shubhankar Kulkarni
Shubhankar Kulkarnia month ago
Povilas S Good to hear that you have some experience with it. So you actively inhale salty water instead of the passive Jalneti way. I don't think the two ways will lead to much of a difference in the changes brought about in the physiology and immunity due to nasal irrigation. So, the results obtained by both these techniques should be comparable. I have a few questions:

1. How much salt do you use?
2. When you started doing it and had no experience, how did you manage to inhale it with the right intensity so as to avoid it reaching places that cause pain/ irritation? Does it still cause pain?
3. Do you inhale with one nostril at a time? If yes, does the solution enter the other nostril or your mouth internally?

To answer your question, saline contains about 0.85% salt. This solution is considered isotonic to both the human body and the bacteria, which means that it cannot kill the bacteria. So it is generally advisable to use a higher salt concentration for gargling, about 1%. Non-halophilic bacteria might get killed at this concentration. [1] However, a higher salt concentration for nasal irrigation might cause irritation and even headache. So, here is my dilemma. Those who perform Jal neti have always noted using the isotonic solution. I have never come across a report of the use of a higher concentration for nasal irrigation. What is, then, the use of salt while performing Jal neti?

References:
1. https://sciencing.com/effects-salt-concentration-bacterial-growth-5924409.html
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Povilas S
Povilas Sa month ago
Shubhankar Kulkarni "What is, then, the use of salt while performing Jal neti?". It's probably mostly for reducing the irritation of the lining of the nostrils. Salt works very well for this. Without it, the experience is pretty much like diving in a lake without any mask. I didn't expect that salt can take the irritation away, so I was very surprised when I did it the first time, I thought it's going to be even worse. But it's bearable even without salt and you get used to it. I sometimes rinse the nose with freshwater too.

I use about 0.5 tablespoon of salt for a cup of water, maybe less. In fact, I add the salt, sometimes rinse my mouth to test the taste, or not, so I don't count exactly. And I keep diluting the solution with additional freshwater while performing the process. But I think it's more than 1% solution. If it's too little, then it's irritating, but if it's too much then also, you might get a sort of burning sensation in the nostrils and a bitter taste in your mouth. So there's a certain optimal range. Maybe I should count the upper and lower concentrations of that range just for interest. But the solution I can still tolerate I think is pretty strong.

So to answer your second question - it was pretty easy because it didn't cause any irritation compared to freshwater rinsing, which I had tried before. And no, it doesn't cause pain if the concentration is right. It might still be a bit irritating, but nothing like freshwater.

Yes, I mostly inhale with one nostril at a time. The solution partly enters the other nostril and partly the mouth, but mostly it stays in the same nostril. And that's why I think the original Jal neti practice should be more effective. It should cleanse your nasal passages much better. I think it's comparable to rinsing a dirty dish under a stream from the tap vs rinsing it by pouring water from your hand on it. I think it's not without a reason it is originally practiced this way.
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Shubhankar Kulkarni
Shubhankar Kulkarnia month ago
Povilas S Right! Even I think that the purpose of adding salt is to make the solution isotonic and, thereby, reduce the irritation. However, I also think that the effect of Jalneti on reducing infections and allergies goes beyond simple cleansing of the nasal passage. I think the irritation modulates the players of the immune system (don't know how) and optimizes the immune response. This is just a theory though. Freshwater is not isotonic and, therefore, causes mild irritation, which might have some benefit.

You mentioned that you feel a bitter taste in your mouth if there is too much salt in the solution. Any idea why bitter and not salty?

Nasal irrigation using saline decreases nasal histamine and LTC4 concentrations

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Shubhankar Kulkarni
Shubhankar Kulkarni Mar 04, 2021
A study tested the effects of nasal irrigation using one of the following solutions: 1. heated water particles at 43 degrees C, 2. heated molecular water vapor at 41 degrees C, and 3. simple saline solution. The authors found that all three types of nasal irrigations decreased (not all treatments showed a significant decrease) nasal histamine concentrations immediately after the treatment and the effect stayed for up to 6 hours. The largest drop in the histamine levels was observed 2 hours after nasal irrigation using the simple saline solution. The histamine levels dropped from about 55 ng/ml to about 10 ng/ml.

The concentrations of Leukotriene C4 (LTC4), another inflammatory mediator, were studied and found to drop significantly after 30 minutes of nasal irrigation using simple saline and the effect stayed up to 4 hours. Since histamine is majorly produced by mast cells and basophils and LTC4 is produced majorly by eosinophils and neutrophils, it is likely that the concentrations of these cells in the vicinity decrease, too.

[1]Georgitis JW. Nasal hyperthermia and simple irrigation for perennial rhinitis. Changes in inflammatory mediators. Chest. 1994 Nov;106(5):1487-92. doi: 10.1378/chest.106.5.1487. PMID: 7956408.

Elevation in intranasal temperature by nasal irrigation using water vapor reduces the symptoms of rhinitis

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Shubhankar Kulkarni
Shubhankar Kulkarni Mar 04, 2021
A double-blind, randomized, placebo-controlled clinical trial enrolled 78 patients who had perennial rhinitis. They were subjected to a hot saturated air (water vapor, 42 degrees C to 44 degrees C) treatment or a room temperature air (20 degrees C to 24 degrees C) treatment. Each treatment consisted of three 30-minute sessions and the patient's subjective responses (daily symptom score) were recorded during the following week. The second treatment was given a week later and the same response recording method was followed. Nasal patency (maximal nasal expiratory and inspiratory airflow and area covered with vapor formed by the exhaled air on a plate) was determined before and after the treatments. The results were found to be reproducible using all three methods. The elevation of intranasal temperature using nasal irrigation by water vapor resulted in the amelioration of perennial rhinitis symptoms. This was demonstrated using all three tests performed. Nasal patency increased in a significant percentage of patients compared to the placebo-treated (room temperature air) group.

The beneficial effects of heated water vapor in treating chronic rhinitis maybe because the heated vapor, probably, added fluid to the mucosal surface and reduced the cellular mediator (histamine, Leukotriene C4, and other inflammatory molecules) release. Also, the heat may interfere with mast cell-allergen or basophil-allergen interactions reducing the release of the inflammatory molecules. It is also suggested that the vapor may help stabilize the mucosal surface by reducing glandular secretions via a decrease in vascular permeability.

[1]Ophir D, Elad Y, Fink A, Fishler E, Marshak G. Effects of elevated intranasal temperature on subjective and objective findings in perennial rhinitis. Ann Otol Rhinol Laryngol. 1988 May-Jun;97(3 Pt 1):259-63. doi: 10.1177/000348948809700309. PMID: 3288075.

[2]Georgitis JW. Nasal hyperthermia and simple irrigation for perennial rhinitis. Changes in inflammatory mediators. Chest. 1994 Nov;106(5):1487-92. doi: 10.1378/chest.106.5.1487. PMID: 7956408.

Viral replication rate decreases at higher temperatures

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Shubhankar Kulkarni
Shubhankar Kulkarni Mar 05, 2021
Another reason why nasal irrigation with saturated water vapor works in mitigating the symptoms of a viral infection can be that the replication of the virus decreases at supra-optimal temperatures. An old study demonstrated the effect of different temperatures on viral RNA synthesis in vitro. Please check figure 2 from reference , which shows that the viral RNA synthesis rate is the highest at 36 degrees C. and decreases gradually as temperature increases. At 39.5 degrees C., the curve is almost flattened leading to minimal viral RNA synthesis and replication.

Nuclease (produced by lysosomes) degrades RNA and stops further synthesis. Nuclease is present in the infected cells, even at 36 degrees C. However, the activity of the nuclease is masked by the speedy replication of the virus. At higher temperatures, viral replicase is inhibited and the RNA in the infected cell is degraded by the nuclease. Although upon infection, leukocytes surround the infected cells and secrete inflammatory molecules and pyrogens that increase the body temperature, additional external heat is beneficial to stall viral RNA synthesis.

A randomized double-blind trial demonstrated that inhaling fully humidified air at 43 degrees C gave more benefit to patients suffering from cold than inhaling air at 30 degrees. Patients having typical acute nasal and upper respiratory symptoms without a history of allergic diseases breathed from apparatus delivering 40 liters per minute of fully humidified room air heated to 43 degrees C or 30 degrees C. The severity of symptoms in patients treated for 20 minutes at 43 degrees C reduced to half than that of those treated at 30 degrees C. Nasal hyperthermia could improve the course of a common cold.

[1]Lwoff A. Death and transfiguration of a problem. Bacteriol Rev. 1969;33(3):390-403.

[2]Tyrrell D, Barrow I, Arthur J. Local hyperthermia benefits natural and experimental common colds [published correction appears in BMJ 1989 Sep 2;299(6699):600]. BMJ. 1989;298(6683):1280-1283. doi:10.1136/bmj.298.6683.1280

Nasal irrigation using a saline solution improves anti-oxidant and antimicrobial activity 6 to 24 hour later

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Shubhankar Kulkarni
Shubhankar Kulkarni Mar 05, 2021
Nasal secretions contain antimicrobial peptides like lysozyme and lactoferrin that form an important part of innate immunity. The antimicrobial activity of subjects suffering from chronic rhinosinusitis and healthy volunteers was studied. It was found that antimicrobial activity in nasal secretions was reduced in the chronics rhinosinusitis patients although there were comparable concentrations of antimicrobial peptides. The reason behind this might be the diluted nasal secretion due to increased water content in the patients.

The volunteers were divided into groups and each group was subjected to nasal irrigation using a different solution. Lysozyme and lactoferrin concentrations and the antimicrobial activity of the nasal secretions were measured at 0, 1, 6, and 24 hours after irrigation. Isotonic (0.9% Na) nasal irrigation reduced the lysozyme and lactoferrin levels initially, which returned to baseline by 6 hours but the antimicrobial activity returned to baseline at 24 hours. Low-salt (0.0375% Na) solution increased Lysozyme and lactoferrin concentrations in the secretion by approximately 40% at 6 hours and 24 hours, but there was a transient decrease in antimicrobial activity that returning to baseline levels by 6 hours. The hypertonic solution increased lysozyme and lactoferrin levels by approximately 30% at 24 hours and there was no change in the antimicrobial activity.

The results suggested that low functionality rather than low levels of antimicrobial peptides may be a contributing factor to the pathophysiology of chronic rhinosinusitis. The low functionality can be due to an increased secretion volume (water and bicarbonates), which hinders the antimicrobial activity of the peptides. The reason behind the hypertonic solution showing no initial decrease in the antimicrobial activity may be due to the fact that salt content in the solution itself may act as an antimicrobial substance.

[1]Woods CM, Tan S, Ullah S, Frauenfelder C, Ooi EH, Carney AS. The effect of nasal irrigation formulation on the antimicrobial activity of nasal secretions. Int Forum Allergy Rhinol. 2015 Dec;5(12):1104-10. doi: 10.1002/alr.21604. Epub 2015 Jul 24. PMID: 26205877.

Ciliary beat frequency: An important mucosal clearance parameter that is different in allergic rhinitis and chronic sinusitis

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Shubhankar Kulkarni
Shubhankar Kulkarni Mar 17, 2021
We have established a difference in the pathophysiology of perennial allergic rhinitis and respiratory infections. There are also differences in the non-pathogenic diseases like perennial allergic rhinitis and chronic sinusitis. Both these diseases have medications that treat the symptoms and these medications do not necessarily cure the diseases. Hence, there is a need for treatments that can cure the disease. Antibiotics are prescribed in chronic sinusitis but they are to prevent/ treat the infection arising from the sinusitis and not sinusitis itself.

The ciliary beat frequency is the native frequency at which the cilia in the respiratory tract move in a wave-like fashion to move the mucus from the inside towards the nose/ mouth. This movement of the cilia helps discharge the mucus created by the Goblet cells and thereby, throws out pollutants and pathogens that enter the respiratory tract.

It is suggested that perennial allergic rhinitis and acute sinusitis are less likely to cause permanent epithelial structural damage and ciliary loss, and therefore, a change in ciliary beat frequency is not expected. In cases of these two diseases, the amount and the properties of the nasal secretions contribute to the temporary impairment of mucociliary clearance. On the other hand, chronic sinusitis is characterized by chronic low-grade infections. They may give rise to permanent ciliary dysfunction and structural changes in the epithelium. Electron microscopy studies have demonstrated ciliary disorientation, loss of ciliated epithelial cells, and an increase in nonciliated cells in chronic sinusitis patients. Ciliary clearance is dependent on the severity of sinusitis. The more severe the chronic sinusitis, the more delayed the nasal mucociliary clearance time.

A study in patients with non-pathogenic respiratory diseases demonstrated that mucociliary clearance time decreased in perennial allergic rhinitis and acute sinusitis patients on nasal irrigation with isotonic NaCl solution. On the other hand, the mucociliary clearance time in patients with chronic sinusitis decreased with nasal irrigation using hypertonic NaCl solution (3%, pH 7.6 for 10 days). Hypertonic solution did not reduce the mucociliary clearance time in perennial allergic rhinitis and acute sinusitis patients and the isotonic soluiton did not reduce the mucociliary clearance time in the chronic sinusitis patients. Hypertonic solution stimulates ciliary beat frequency and, thus, restores the main impaired mechanism causing mucociliary clearance delay. Hyperosmolar fluid in the airway causes the release of calcium and prostaglandin E2 from intracellular stores, increasing the availability of adenosine triphosphate (ATP) to the cilia axoneme, resulting in increased ciliary beat frequency (cilia require ATP to beat). Here is another study showing the beneficial effects of nasal irrigation using hypertonic saline in chronic sinusitis patients.

So, the ciliary beat frequency can be one of the mechanisms that is modulated by nasal irrigation that can lead to optimum mucus movement and discharge leading to a healthier condition.

[1]Ural A, Oktemer TK, Kizil Y, Ileri F, Uslu S. Impact of isotonic and hypertonic saline solutions on mucociliary activity in various nasal pathologies: clinical study. J Laryngol Otol. 2009 May;123(5):517-21. doi: 10.1017/S0022215108003964. Epub 2008 Oct 28. PMID: 18957157.

[2]Talbot AR, Herr TM, Parsons DS. Mucociliary clearance and buffered hypertonic saline solution. Laryngoscope. 1997 Apr;107(4):500-3. doi: 10.1097/00005537-199704000-00013. PMID: 9111380.

How nasal irrigation using solutes other than Na and Cl affect the respiratory tract

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Shubhankar Kulkarni
Shubhankar Kulkarni Mar 17, 2021
The benefit of nasal irrigation is further increased by the addition of ions different from Na+ and Cl− because they can exert a relatively positive effect on epithelial cell integrity and function.
  1. Magnesium: It promotes cell repair and limits inflammation by reducing eicosanoid metabolism. Magnesium inhibits exocytosis from permeabilized eosinophils (that secrete histamine) and, together with zinc, reduces apoptosis of respiratory cells.
  2. Potassium: It reduces inflammation and increases the viability of respiratory cells.
  3. Bicarbonate ions: They reduce mucus viscosity. However, they also increase the pH of the solution. Although in vitro studies have shown that acidic pH can reduce the ciliary beat frequency, whereas the opposite occurs when slightly alkaline solutions were used, in vivo use of a solution with pH ranging from 6.2 to 8.4 did not affect mucociliary clearance.
In general, nasal irrigation clears microbial antigens and inflammatory mediators and dislodges (and indirectly replenishes) the mucus lining.

[1]Principi N, Esposito S. Nasal Irrigation: An Imprecisely Defined Medical Procedure. Int J Environ Res Public Health. 2017;14(5):516. Published 2017 May 11. doi:10.3390/ijerph14050516

Why not use animal models to test the hypothesis?

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Subash Chapagain
Subash Chapagain Mar 03, 2021
Like other medical interventions deemed to have therapeutic/preventive potential, we can use small animal models in the laboratory to test this theory as well. Rodents and rabbit models could be the best to start with as they are relatively easy to handle. One concern would be to obtain the humanized mouse models for the test. However, given the wide-scale research post covid-19 pandemic, this should not be impossible.
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Povilas S
Povilas Sa month ago
Why not use animal models - because it raises ethical concerns like all experiments involving animals. Humans can volunteer, animals are forced into it.
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Subash Chapagain
Subash Chapagain2 months ago
Using different concentrations of varying salinity, and negative controls, we can test whether this works or not. I think we would have to first optimize the viral infection process for the animals to be used. Also, it would be better to test different viral loads (amount) in the aerosol and if this approach actually works, what is the threshold of the viral load that it can effectively check.

If these preliminary tests yield any positive results (that is prevention of infection/ lower level of infection than the control), then we can further investigate the molecular/cellular level mechanisms. In my opinion, shall this ever work, it would mostly have to do with the reduced viral attachment as a result of the irrigation. To examine this, we can drop down to in vitro assessments. One approach would be to culture mucous cells ( I am not sure about their culturability though) and then test the viral capacity to infect them with and without saline irrigation.
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Shubhankar Kulkarni
Shubhankar Kulkarni2 months ago
Yes, animal models can be used. I am thinking of the experiments that can be performed using the animals to prove our/ alternative hypotheses.

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General comments

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Darko Savic
Darko Savica month ago
Shubhankar Kulkarni from your experience, does jal neti treatment have any effect on the irritation of mucous membranes of the eyes?
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Shubhankar Kulkarni
Shubhankar Kulkarnia month ago
Darko Savic Yes. For me, Jalneti (I do it using warm water, no salt) reduced sneezing, rhinorrhea, and eye irritation. I feel nasal congestion just after performing Jalneti but that goes away in about 15 to 20 minutes. After that, I don't feel the above symptoms for the rest of the day. Rhinitis is worst in the mornings; so I perform Jalenti then. I find that using warm water is key. I have tried it without warming the water or with lukewarm water. Although these methods are beneficial, they are not as good as that with warm water.
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Darko Savic
Darko Savic2 months ago
From experience, I can tell you that during the presence of an allergen like pollen, the amount of water that comes out of one's own mucous membrane is almost 20% of what the Jalneti video showed. It's like walking around with a dripping tap on your head:) The body washes out the allergen pretty efficiently. The difference between Jalneti removal and the body's own removal could be measured to a few minutes at best. The main problem is the continued presence of allergens in the inhaled air. As soon as any kind of washing is done, new allergens are inhaled with the next breath and the vicious cycle continues. It would take something like this to provide continuous relief https://youtu.be/6UkzMN-Jvd0?t=102

The allergy season is starting in Europe. I will try the Jalneti washing method. My hunch is that it won't make a difference that lasts more than a few minutes outdoors. My baseline is on antihistamines. Without them it would be a nightmare test
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Shubhankar Kulkarni
Shubhankar Kulkarni2 months ago
Darko Savic I tried Jalneti last year, and I noticed a reduction in sneezing. I agree that flushing out of the allergens is not the only action of nasal irrigation that helps; it probably does much more than that. I want to focus on the latter part. I think it modulates the immune response, brings it to the optimum level. I am trying to figure out a way of testing this at home.

Yes, do try it. Start atleast a couple of weeks before the season starts. If you haven't done Jalneti previously, start another week prior. It took me a week to do it properly. The first week is painful. Your eyes water, you feel pain in your forehead, and you feel nasal congestion. (The same feeling when you learn to swim). All these symptoms are temporary, they vanish within an hour of performing Jalneti. Once you master it, these symptoms start subsiding gradually.

If you take anti-histamines regularly, have you noticed a decreased efficacy over time? The dose that got me through a day increased. It is probably something like resistance towards the drug.
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Darko Savic
Darko Savic2 months ago
Shubhankar Kulkarni desloratadine seems to work better than loratadine for me. The dosage is also smaller. I take it in the evening to minimize the sleepiness throughout the day.

For me, there are a few days (1-14) in every season when it seems that no dosage of antihistamines would help. On rare occasions, I double the dose but reduce it again as soon as I feel better. I didn't attribute it to a buildup of tolerance. Rather I think it's just the top season for a specific type of pollen and it takes a few days for it to subside.

The season here has started a month earlier due to a very warm winter. I better find a teapot quickly:)