A breakthrough in the fight against COVID-19. A pilot-scientist from Poland discovered how to inhibit symptoms. Doctors confirm

Tomasz Raudner, ŚląskiBiznes.pl .: Mrs. Magdalena, the world is looking for effective methods to fight COVID-19. You claim that you found a mechanism for the development of the disease. How could this affect the treatment of covid patients? 

Magdalena Filcek (bio - see photo gallery): I am also surprised by what I discovered (link to complete science research). I did not expect this. As a scientist, I was looking for technical data on the operation of ventilators to answer the question why the death rate is so high when patients are connected to them. This path gave direction to my research and allowed me to make unexpected observations, that in the case of COVID-19, there is a pathophysiological mechanism that invokes symptoms that are confusingly similar to those of the "histamine storm" that, so far,  has not been considered.

What is a histamine storm?

Its key is the activation of mast cells and the release of histamine from them, which acts as an intermediary in the onset of inflammation in the body. The goal of histamine and the inflammatory reactions it causes is to defend the body, limit its action, destroy and remove the cause, and repair the resulting damage, but when its release is too rapid and / or chronic, it can become one of the factors of anaphylactic shock, organ damage, serious complications and life threatening.

What exactly does histamine have to do with COVID– 19? What is the histamine?

According to my theory, SARS-CoV-2 as an environmental factor and an external trigger, when it enters the body, it initiates the activation of mast cells in the lungs as a consequence of releasing a large amount of histamine. This, in turn, affects a set of specific receptors: H1, H2, H3, H4 and causes an allergic and pseudoallergic reaction called histamine intolerance.As a trigger, histamine provoke a chain of successive stages of the inflammatory reaction that lead to the so-called hyperimmune response, systemic inflammatory reaction syndrome, and multi-organ failure. The highest concentration of histamine appears in the skin, lungs, nasal mucosa and stomach. Avalanche histamine ejection and stimulation of the above-mentioned receptors leads to, among others: bronchospasm, cough, shortness of breath, increase in blood clotting, decrease in saturation, tachycardia, vasodilation and increase in their permeability, edema, diarrhea, pressure drop, characteristic severe fatigue, fever, headache, neurological changes, such as also for multi-organ inflammation in the lungs, intestines, heart, kidneys and liver, among others. The same symptoms of the systemic inflammatory reaction above are also observed in developing COVID-19 and its complications, this observation was a clue for me to discover its mechanism.

How come no one paid attention to the role of histamine in the course of the disease?

Sometimes we are looking for something very deeply and the solution may lie in front of our eyes because "it seems too simple to be true ...". I, too, did not believe this discovery at first, but the medical science and the laws of physics spoke clearly and forcefully, it was difficult to ignore them.

First, the lungs are full of mast cells, which are multifunctional cells and belong to the family of white blood cells. They are formed in the bone marrow and reside in the tissues of the entire body, especially under the skin surface, near blood and lymph vessels, within nerves, in the mucous membranes of the respiratory tract, gastrointestinal tract and urinary tract. These mast cells are part of the immune and neuroimmune systems and are involved in the body's defense against pathogens. Their activity is primarily caused by biological factors, such as bacteria, fungi, protozoa, parasites or viruses, chemical factors such as toxins, poisons, corrosive substances, various foods, and changes in pH. Also physical causes: cold, heat, pressure, vibration, ionizing radiation, electromagnetic fields, ultrasound waves, and various types of mechanical effects on the body can make mast cells become hyperactive. The same may be the case when a group of pathogenic microorganisms produces various defense mechanisms against the drugs we take, including antibiotics, which make them very difficult to fight, and this may also be the cause of these processes. We generally call them alarm factors. And let's not forget about psychological factors - such as stress.

What do mast cells have in common with histamine?

Activation of mast cells starts the degranulation process and the release of substances contained in them or synthesized anew from the grains: histamine, heparin, proteases, leukotrienes and cytokines / chemokines. Their primary role is to induce local inflammation (including allergies or pseudoallergies) in response to external or internal factors. In response to microbial attack, as well as selected chemical and physical factors, mast cells can react violently, releasing substances with a strong defensive and vasoconstrictive effect, including a large amount of histamine. 

Histamine exerting physiological effects through its four G-protein coupled receptors H1, H2, H3, H4, getting into the bloodstream, causes systemic inflammatory reaction syndrome and multi-organ failure, anaphylactic shock, life-threatening or even death; in chronic cases, it may initiate autoimmune diseases. Research results also suggest that histamine released from mast cells may play a key role in high blood clotting, the pathogenesis of pneumonia, myocarditis, and neurogenic inflammation, which are very common symptoms in COVID-19.

What brought you to this trail?

Paradoxically, respirators contributed to noticing the mechanism of action of histamine in COVID-19. My parents contracted COVID-19 at the end of January 2021, both had pneumonia and were hospitalized. Mom recovered after 3 weeks, but Dad's condition worsened and he was taken to the pulmonary hospital, where after a week he was put into a coma, his muscles relaxed and he was connected to a respirator. On the one hand, it is very lucky that a respirator was available, and on the other hand, the statistics on the deaths of COVID-19 patients placed under a ventilator in Poland were terrifying, the media reported that there were about 90% of them and that this was probably due to too high mechanical air pressure, which can damage the alveoli in the lungs. When I found out that my Dad had a 10% chance of survival, I decided to do everything to make the probability higher. Even one or two percent more could make Dad live. 

I started looking for why the statistics were not the opposite - I wanted to understand this and thus help Dad survive mechanical ventilation. Reading about the history of respirators, I learned that the first idea for a respirator mechanism was invented by Leonardo da Vinci, but the first truly functioning respirator, made in the early 80s of XIX century, was an invention of Jean-Francois Pilatre de Rozier. This name totally surprised me, as I was very familiar with it in the field of aviation, it was the first man in history to rise in a balloon. Intrigued by what he had to do with respirators, I began to study his biography and it turned out that he was a great French inventor and teacher of chemistry and gas physics, who also created diving devices and a balloon control mechanism and personally checked whether the invention worked by becoming the same first pilot of hot air balloons. I took it as a valuable coincidence - because I am also a pilot and mechanic of these aircraft, a scientist and an inventor. 

I began to wonder and analyze whether in a way known to me from aviation and aerostatics it would be possible to lower too high mechanical pressure from the respirator by replacing it with the physical properties of gases. As a pilot, I am familiar with Charles's Law, which describes the principle that allows balloons to float in the air by using only air heating and differential temperatures and pressures. I began to naively think of the lungs as balloons and wondered if the warm air filling the lungs would support the lifting of the ribs and sagging muscles. 

Following this thought, I learned that the ideal temperature for good gas exchange in the lungs is the air temperature of 37°C and 100% humidity, i.e. about 44 mg H2O / L, then I asked the doctors what the current temperature of the gas mixture reaching the lungs of the patients from the ventilator and I was informed that it is probably "room temperature" which is around 20ºC - 26ºC. 

I was surprised that this is well below the level needed by the lungs for good oxygen-CO2 exchange, especially since this low air temperature is also not able to provide the correct level of humidity for the lungs. Moreover, according to Charles' law, the pressure and / or capacity of air delivered by a ventilator at a temperature of approximately 20ºC - 26ºC will increase - when it begins to heat up in the lungs to a body temperature of 37ºC. This can cause a lot of damage including damage to the alveoli and through the cold and excessive pressure the activation of mast cells that are massively present in the lungs. We should also remember that the patient's body will also cool down and dehydrate, giving up its heat and H2O to heat and moisturize the cold, dry air that is forced in. 

Wait, it turns out that connecting to a ventilator is harmful to COVID patients. 

The consequence of the unstoppable cascade of the histamine reaction in response to pathogens and other factors is, among others, bronchospasm, coughing, a decrease in oxygen saturation and breathing difficulties observed in the symptoms of COVID-19 and, as acute respiratory failure, in many cases leads to the need for oxygen therapy, and in the advanced stage to mechanical ventilation, which very often leads to ventilator / secondary pneumonia (VAP).

It seems that improperly applied invasive mechanical ventilation of a patient may additionally, unintentionally, aggravate the pathophysiology of a patient with COVID-19. Intubated patients with the aerodynamics of the nasal flow bypassed, in many cases they are ventilated with cold and dry air, taking into account the difference in its temperature with the patient's body temperature, according to the law Charles Charles, while heating up in the lungs, this air additionally reaches excessively high pressure, these physical factors can activate nonspecific degranulation of mast cells and the release of further doses of histamine, leading to pulmonary damage, lung inflammation, fibrosis and barotrauma, a systemic inflammatory reaction that also occurs in the case of COVID-19, and against which doctors are powerless.

It should be noted that the passive heat and moisture exchanger used in some cases with respirators, the so-called HME will not deliver the required physical parameters of the air into the lungs during mechanical ventilation. It is worth considering adding and replacing the passive exchanger - an active moisture heater (HH) as a required device in each ventilator to heat and humidify the air to the required levels. It would also be necessary to verify the air volume setting to the specific mass, not the total body weight of the patient. 

The temperature and humidity of the supplied air is very important not only when the patient is connected to a ventilator for a long time, but also during several hours of surgical procedures where unintentional hypothermia caused by low air temperature from the ventilator may cause the release of histamine along with the activation of blood coagulation. Scientific studies indicate that the frequency of body temperature below 36 C may affect 50–90% of ICU patients. Healthcare authorities around the world recommend actively warming the patient as an "inflammatory prevention step" (which, as we already know, may come from a storm of histamine, provoked, for example, from cold as well as air pressure from a ventilator). 

In addition, I noticed that the symptoms of the above-mentioned occurring with HIT (Histamine Intolerance) and COVID-19, are very similar to SIRS and SEPSY - which gives me grounds for expanding the hypothesis that antihistamines, displacing histamine from connections with receptors, may have a much wider application and be a complementary confirmation of finding the right mechanism for symptoms for COVID-19, SIRS and SEPSY of storm-induced histamine intolerance syndrome. Referring to the presented mechanism of COVID-19 inflammation inducing multi-organ dysfunction, including the pro-thrombotic stage, hypercoagulability, cytokine storm and direct vascular damage; I suggest the role of the histamine mechanism as an important cause of the systemic inflammatory reaction syndrome, and as prevention and help in its treatment - antihistamines, which can also support venous thromboembolism. 

Does this mean that those suffering from COVID -19 suffice to take allergy pills?

Yes, it is possible, if they are drugs with antihistamines. Their administration is certainly, in accordance with the principle of "primum non nocere" - it will not hurt, it is important to know which antihistamines are the best in this case, e.g. a second-generation H1 receptor antagonist, and in what dose, depending on whether we are talking about prevention or supporting the treatment of the symptoms of the disease.

COVID -19, as an invisibly spreading infection, makes mankind look forward to a highly safe medical agent that can be used by a wide range of patients. The observations carried out in the UAE, India and Poland, as well as studies from the USA, seem to confirm the success of this hypothesis in the rapid treatment of COVID-19 with antihistamines that are safe, widely available, cheap and approved for many years. They have been used for decades even in children, their safety is undeniable, and the observations have additionally confirmed their effectiveness. Based on the literature available to date, both in the field of COVID-19 and the treatment of patients with viral diseases, idiopathic mast cell activation syndrome, histamine intolerance, as well as consultations with many specialists in the field of pulmonology, anesthesiology, allergology, physics, chemistry, and technical issues of ventilators, genetics, from published studies on histamine, it can be concluded that antihistamines blocking H1-H4 receptors, used preventively at the first symptoms of dyspnea and during the development of the disease, can stop the cascade of reactions in the form of a histamine-cytokine storm, and thus the progression COVID-19 and prevent many patients from mechanical ventilation. The administration of well-selected antihistamines (depending on the effect on the selected H1-H4 receptor) can prevent many people from being hospitalized in emergency departments and reduce the death rate due to COVID-19. 

My hypothesis is confirmed by the observations published in the media that people with asthma or allergies who take antiallergic drugs (i.e. antihistamines) either do not suffer from COVID -19 at all or undergo it very mildly. This also agrees with a study from the University of Florida, where researchers found that COVID-19 patients who were taking antiallergic drugs with antihistamines due to allergies or asthma had very mildly recovered the disease. They confirmed the effectiveness of antihistamines in laboratories, although they indicated that they do not know what the mechanism is and why these drugs help. Supporting scientific solidarity, I sent my hypothesis to the UF scientists so that by joining forces and knowing the mechanisms, we could help people faster. 

Amantadine also contains an antihistamine. In addition, attention should be paid to the level of histamine neutralizing enzymes in the body, such as DAO and HNMT, provide them if possible and support their synthesis with supplementation. Of course, applying the presented hypothesis does not automatically guarantee obtaining the same results in all patients, and further extensive research work involving randomized controlled trials should be carried out on a large number of COVID-19 patients in order to establish the exact role of histamine and the beneficial effects of targeted (depending on the receptors), antihistamines to prevent hypercoagulability, inflammation and organ damage caused by COVID-19. Scientific research suggests that antihistamines can also reduce various stages of the inflammatory process of myocarditis. 

You mentioned that many specialists support this theory. Who? 

I consulted the details of my discovery with over 50 specialists in their fields at home and abroad, in addition, I sent my hypothesis to first-line pulmonary specialist Dr. Mayank Vats from Dubai, who verified that administration of antihistamines was actually helping his COVID-19 patients. In the meantime, I also contacted Dr. Mirosław Mastej, a specialist in min. from HIT to consult the details of histamine and the possibility of its neutralization in the body, as well as with the head of the anaesthesiology and intensive care department - anesthesiologist Dr. Anna Skrzyniarz-Plutecka, in order to verify the parameters of mechanical ventilation (e.g. temperature and humidity of the air mixture) in ventilators and to confirm the hypothesis about the effect of antihistamines in post-covid patients, also during surgery with mechanical ventilation. 

The first cases / observations based on my hypothesis in the United Arab Emirates, India and Poland show that antihistamines have a beneficial effect in the symptomatic treatment of COVID-19, can serve as prevention and adjuvant therapy in severe COVID-19 with chronic multi-organ symptoms, also in patients before, during and after operations. Above doctors were very positively surprised by the excellent results they achieved in patients using antihistamines. 

At this point, we present the opinions of the three specialists mentioned by you.  For start, Dr. Mayank Vats (bio - see photo gallery): 

"Thanks to Ms Magdalena's hypothesis and her extensive research work on the role of histamine in the release of the inflammatory cascade in Covid-19, and through regular scientific discussions with me and many prominent physicians and scientists, I began using the antihistamine cetirizine on a regular basis in almost all patients. and I have seen significant beneficial results with fewer symptoms such as throat irritation, coughing, shortness of breath, and I would even say a faster recovery from COVID -19 during the second wave. I have noticed that there is a marked improvement in virtually all mild, moderate or severe cases of the disease, without any significant side effects from antihistamines.

I am lucky that Magdalena has discussed with me every aspect of the antihistamine drug and the potential benefits for COVID-19 patients, and thanks to the scientific facts she found and persistence, we have used it regularly on almost all patients in India and at my hospital in the United Arab Emirates and we have had impressive positive results." 

Now the opinion of Dr. Anna Skrzyniarz - Plutecka (bio - see photo gallery):

“Antihistamines are probably not a panacea for everything, but they are definitely worth attention and further research on their use in patients undergoing mechanical ventilation in the ICU and during surgery. One of the pathways presented in the hypothesis by Magdalena Filcek is the mechanism of histamine release from mast cells in the lungs under the influence of mechanical ventilation. In most cases, artificial ventilation is based on the supply of a mixture of gases at room temperature and reduced humidity to the patient's lungs (physiologically, our lungs have a temperature of 37 C and 100% humidity). As standard, respirators and anesthesia machines are not equipped with active heat and moisture exchangers, heaters or air humidifiers. 

This state of affairs may cause the release of histamine from mast cells in the lungs of patients and, consequently, lead to a histamine-cytokine storm - its result may be bronchospasm, an increase in platelet aggregation and a decrease in saturation, and even damage to the lung parenchyma and barotrauma. Advance administration of antihistamines can be effective in counteracting this reaction by reducing respiratory complications in mechanically ventilated patients. A probable and systemic solution to this issue could also be a change in the standards for the equipment of anesthesia machines and ventilators - I mean ventilation based on warm and properly humidified air. 

After getting acquainted with the mechanism described by Mrs.Magdalena and thoroughly analyzing it, I implemented antihistamines for prophylaxis and treatment with very good results, increasing the safety of ventilated patients procedure both in the Intensive Care Unit and during surgeries. In my opinion, the hypothesis described by Ms Magdalena, and in principle thesis, is correct and should inspire the medical community to change the standards of dealing with patients undergoing mechanical ventilation." 

And now dr Mirosław Mastej:

For over a dozen years I have been interested in the medical and scientific research of histamine and its physiological and disease role. In the spring of 2020, I found an English publication describing disastrous results of treatment with ventilators. 

There was 70-80% mortality among those who undergo such treatment and put into pharmacological coma. Only the contact with the amazing Magda Filcek and a conversation with her about gases, expansion, heat, air humidification gave me a partial answer "where is the catch-error, problem". Of course, every doctor in college or high school learned the laws of physics, and these are obvious things! It's just that you still need a "genius" or "spark" of thought to connect it with each other. And Mrs. Magda shone with such a spark. Usually, the anesthesiologist connects a person "with healthy lungs" to a ventilator, for example after an accident, on time and after surgery under anesthesia, after a stroke, heart attack, etc. But the lungs, pulmonary alveoli, bronchioles are efficient, "strong" and able to withstand "cold and unhumidified" air, respectively (see article for details). In Covid-19 infection, what the anesthetist put it to me is "semi-liquid pulp"! There is edema (water) in the lung parenchyma. One lung has about 300 million follicles, and in Covid-19 some of them die, there is inflammation, the aforementioned edema, blood, clots. 

But where does this pulp come from? Is it just the virus behind it? At first, the whole world seemed to think so. Yes, there is the concept of a cytokine storm that this leads to a violent inflammation and a fatal end, but that nothing or little can be done because viral particles are the cause! Well, edema, i.e. the penetration of water from the capillaries, lymphatic or small arterioles into the tissues is caused by histamine (it is a direct mediator)!

Just as our skin "swells" after a bee sting, where histamine locally in minutes can "flood the tissues with water", so also in the lungs! It is a physiological reaction in the event of a sting, because the venom introduced by the insect is locally diluted. So that our defense can neutralize this venom locally. It's a well-known evolutionary defense mechanism. Unfortunately, such a lung defense against the SARS-CoV-2 virus in some people is dramatically excessive and dangerous! And here is this spark of thinking by Magdalena Filcek: noticing that the degranulation of mast cells occurs not only under the influence of e.g. allergens and antibodies, or venoms, various chemicals and even drugs, or viruses (chemical and biological stimuli), but also physical stimuli, i.e. mechanical stretching, squeezing or temperature - which can stimulate such a mast cell to release histamine. Yes, this is a known phenomenon, for example, there are "allergic" reactions to wind, exercise, excessive sweating. We know it on the skin, or even in asthma attacks, but here she asked a dazzling question: what would mast cells do in the lungs, in the mucosa, in the bronchial wall, located in large numbers somewhere between the alveoli, if they got a breath of air a few degrees colder, or pressure higher than usual? My answer was unequivocal! There would be a burst of histamine as a mediator of "help" to other immune cells seeking rescue when something damages us! And so begins a fragment of the cytokine cascade. As a consequence, swelling, inflammation, and microclots. All of this exacerbates the damage caused by the virus. Consequently ... pulp! Were it not for the question of Magdalena Filcek, a brilliant mind from the outside (out of the box), no doctor would probably have thought of it, although they would have circulated close to the solution. 

Blocking the appropriate histamine receptors (in my opinion, necessarily H1, perhaps also H2 and H3, H4, for which there are slightly different, selective antihistamines) should be a standard. The same goes for proper humidification and warming (with appropriate and existing, but not usually used in Poland) respirator attachments! This requires more detailed research, selection of doses, etc. The Nobel Prize will go to Ms Magdalena Filcek for this spark !!! 

We go back to the conversation. Did you share your findings with, for example, the Ministry of Health or other institutions?

As soon as I created the hypothesis, I submitted it with the date of the discovery to the notary and started sending it to many institutions without waiting for publication, because every day counts for me to consider, analyze and introduce the necessary changes as soon as possible for the good of humanity. I sent e-mails to national consultants in Poland, to the Ministry of Health, to the Military Institute of Medicine, to the WHO, to the UN, the EU, to ministries in other countries, to doctors in Poland, the USA, Dubai, Malaysia, the Embassy of Italy, Sweden, and hospitals, universities in Poland, Florida, Stanford, pharmaceutical companies and many other places. The Minister of Health in Dubai confirmed the relevance of the discovery and use of ventilator heaters and antihistamines, the Ministry of Health in India faced tragedy during the COVID-19 summit in early May this year. included antihistamines in the official Covid -19 treatment protocol (levocetirizine 5 mg), confirmation of this fact sent by Dr. Mayank Vats: 

“India introduced antihistamines into official governmental Covid treatment protocols following the hypothesis of Magdalena Filcek and the experience of Dr. Mayank Vats. We both had extensive discussions and literature review, including the pathophysiology of Covid affecting the lung parenchyma and the role of histamine and mast cells as a significant mediator of the inflammatory cascade in the lungs and throughout the body, and how to prevent this cascade with antihistamines. Experimentally, a very high beneficial effect of antihistamines was found in almost all patients, so I recommended the Indian government to include antihistamines in the COVID-19 treatment regimen based on the hypothesis and work of Mrs. Magdalena Filcek. She really did a miracle finding a simple remedy that helped tremendously to Covid patients without any significant side effects. She deserves honor of  international organizations for her simple but very effective hypothesis, confirmed and proven by my practical experience being a COVID frontline doctor.”

It is worth noting that the therapy with antihistamines was also successfully implemented by Dr. Anna Skrzyniarz - Plutecka, head of the Department of Anaesthesiology and Intensive Therapy at the Mazowieckie Hospital Oncology in Wieliszew - partner of the Medical University of Maria Skłodowskiej-Curie in Warsaw, with whom I also consulted my discovery. A doctor who agreed with the hypothesis and started using antihistamines in the prevention and treatment of COVID-19 and in patients with lung lesions after contracting COVID-19.

Let me mention that as soon as I found out about the fourth wave in Japan, I also sent the COVID-19 mechanism discovery hypothesis to the local Ministry of Health. I believe that institutions verify the correctness of the hypothesis and if they confirm it, they will be able to include my method as an improvement in the treatment of COVID-19 as well as SIRS and SEPSY, thus reducing the mortality due to the above-mentioned diseases and their complications.

About the treatment. How is Your Dad?

Thank you. Dad spent almost two months on a ventilator, and he stayed for three months in several hospitals. Now he is regenerating at home. I would like to thank all the people with whom I had the opportunity to consult my discovery, for their suggestions, advice and support, and all the doctors fighting for the lives of patients, including my father. I believe that this discovery, at the cost of great pain and a very difficult experience of COVID-19 in my family, will save many people around the world. 

From the perspective of your discovery, what do you think about Poland's purchase of respirators to fight COVID-19? Was it justifiable to bring them? 

I don't feel competent to answer this question. 

Are you still in the field of respirators and histamine?

Yes of course. I am writing a research paper, I already have a reviewer. 

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What is the relationship of this year's Nobel Prize in Medicine with the Polish discovery of the COVID-19 mechanism? Check it out!

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References:

[1] B.T.Elden et al. „The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflamma}on: The Hunt for New Therapeu}c Targets” 13 August 2018
[2] M.E.Parsons, C.R. Ganellin „Histamine and its receptors” January 2006
[3] M.Cataldi et al ”Histamine receptors and an}histamines: from discovery to clinical applications” 22 May 2014
[4] C.A.Akdis,et al. „Histamine receptors are hot in immunopharmacology” March 2006
[5] L. Maintz, N.Novak, „Histamine and histamine intolerance” May 2007 AmJ Clin Nutr. 85(5):
1185-1196
[6] M.Gotz „[Pseudo-allergies are due to histamine intolerance]” 1996
[7] K.Mukai et al. „IgE and mast cells in host defense against parasites and venoms” 25 May 2016
[8] A.B.Kay „Allergy and allergic diseases. First of two parts” 4 January 2001
[9] Dr. D. Jernigan „Histamine Intolerance; The Cause of Hundreds of Symptoms”
[10] „COVID Overview - Symptoms Common Symptoms” CDC Symptom Self-Checker May 2020
[11] Salyers A. A., Whi. D. D.; „Wprowadzenie do chor.b zakaźnych. W: Mikrobiologia. R.żnorodność, chorobotwórczość i środowisko”; Wydawnictwo Naukowe PWN, 2005;
[12] Nicklin J., Graeme-Cook K., Killington R.; “Mikrobiologia – kr.tkie wykłady”; Wydawnictwo Naukowe PWN, 2004;
[13] Red. Nawrot A.; “Encyklopedia Biologia”; Wydawnictwo Greg, 2017;
[14] Salomon E.P., Berg L.R., Mar}n D.W., Villee C.A.; “Biologia”; Mul}co, 2010;
[15] P.J. Barnes „Histamine receptors in the lung” 1991
[16] X.Xiang et al. „Neutrophil histamine contributes to inflamma}on in mycoplasma pneumonia”
December 2006
[17] A.C. Rosa, R. Fantozzi ”The role of histamine in neurogenic inflamma}on” Sept 2013
[18] M. Jutel,et al „Histamine in allergic inflamma}on and immune modula}on” May 2005
[19] W. Lieberman-Cribbin, at al. „The impact of asthma on mortality in pa}ents with COVID-19” 2020
[20] R.S. Hotchkiss et al. „Sepsis and sep}c shock” 30 June 2016
[21] L. Woudstra et al. „Infec}ous myocardi}s: the role of the cardiac vasculature” 14 March 2018
[22] H.Higuchi et al. „Mast Cells Play a Cri}cal Role in the Pathogenesis of Viral Myocardi}s” 7 Jul 2008
[23] A. Matsumori „Myocardi}s: past, present and future” Kitasato Med J 2012; 42 (Suppl): 3-7
[24] A. Matsumori et al. „Ce}rizine a histamine H1 receptor antagonist improves viral myocardi}s” 04 August 2010
[25] P. Webb „Air temperatures in respiratory tracts of res}ngsubjects in cold” Novem 1951
[26] M. Tobi, „Principles and prac}ce of mechanical ven}la}on. 2nd edi}on. 2006. pp. 1109–1115.
[27] H.O.Koskela „Cold air-provoked respiratory symptoms: themechanisms and management” 01 Apr 2007
[28] The Mast Cell Disease Society, Inc. (TMS) „Symptoms and Triggers of Mast Cell Ac}va}on”
[29] D.D.Metcalfe, et al. „Mast cells.” Physiol Rev 1997; 77: 1033–1079.
[30] American Academy of Allergy, Asthma & Immunology „Mast Cell Ac}va}on Syndrome (MCAS)”
[31] M.Frieri, et al ”Mast cell ac}va}on syndrome: a review” February 2013
[32] M.Krystel-Whi.emore et al. „Mast Cell: A Mul}-Func}onal Master Cell” 06 Jan 2016
[33] J.S. Erjef.lt "Mast cells in human airways: the culprit?” 2014
[34] P.Soler et al. „Role of mast cells in the pathogenesis of hypersensi}vity pneumoni}s” Aug 1987v
[35] Ch-E. Luyt, T. Sahnoun, M.Gau}er, et al „Ven}lator-associated pneumonia in pa}ents with SARSCoV-
2-associated acute respiratory distress syndrome requiring ECMO: a retrospec}ve cohort study”
23 November 2020
[36] J.Lee „Hypersensi}vity Pneumoni}s” September 2019
[37] F..lvarez-Lerma, M.Palomar-Mar.nez, et al. „Preven}on of ven}lator-associated pneumonia:
The Mul}modal Approach of the Spanish ICU “Pneumonia Zero” Program* February 2018
[38] M.Maes, E.Higginson, J.Pereira-Dias, et al. "Ven}lator-associated pneumonia in cri}cally ill pa}ents with COVID-19” 11 January 2021
[39] S.Betlejewski et al. „The influence of nasal flow aerodynamics on the nasal physiology” 2008
[40] M.D’Amato ”The impact of cold on the respiratory tract and its consequences to respiratory health” 30 May 2018
[41] M.Wallin et al. „Tidal volumes: cold and dry or warm and humid, does it ma.er?”
[42] G.A.Plotnikow, M.Accoce, et al „Humidifica}on and hea}ng of inhaled gas in pa}ents with ar}ficial airway. A narra}ve review” January -March 2018
[43] J.C. Van Oostdam „Effect of breathing dry air on structure and func}on of airways” July 1986
[44] J.Carvill „Thermodynamics and heat transfer” 1993
[45] S.Wernersson, G. Pejler „Mast cell secretory granules: armed for ba.le” N.R. Immu. 2014; 14:
478–494.
[46] M.L.Taylor, D.D. Metcalfe „Mast cells in allergy and host defense” Allergy Asthma P.2001; 22: 115–119.
[47] A.F. Walls et al „Mast cell tryptase and histamine concentra}ons in bronchoalveolar lavage fluid from pa}ents with inters}}al lung disease” August 1991
[48] M.Metz, M.A. Grimbaldeston, S.Nakae et al. „Mast cells in the promo}on and limita}on of chronic inflamma}on” Immunol Rev 2007; 217: 304–328.
[49] A.St John et al. „Innate immunity and regula}on by mast cells” 1 May 2013
[50] J.Kopeć-Szlęzak „Mast cells and their role in immunity and cancer” 2015
[51] G. Horstmann, et al „Influence of temperature and decreasing water content of inspired air on
the ciliated bronchial epithelium, Acta Oto-Laryn 84, 124–131, 1977.
[52] H.O.Koskela „Cold air-provoked respiratory symptoms: the mechanisms and management” 01
Apr 2007
[53] D.F.Proctor, D.L.Swi..”Temperature and water vapor adjustment. In:Respiratory Defense Mechanisms”
1977, p.95–125.
[54] C.C. W. Hsia et al. ”Evolu}on of Air Breathing: Oxygen Homeostasis and the Transi}ons from Water to Land and Sky” April 2013
[55] D.A.Kaminsky et al. ”Effects of Cool, Dry Air S}mula}on on Peripheral Lung Mechanics in Asthma” 12 June 1998
[56] H.J.M.Lemmens, J.G. Brock-Utne „Heat and moisture exchange devices: are they doing what they are supposed to do?” February 2004
[57] M. Kelly et al. „Heated humidifica}on versus heat and moisture exchangers for ven}lated adults and children” 14 Apr 2010
[58] R. Poopalalingam, M.Goh, Y.W. Chan „The effect of heat and moisture exchanger and gas flow on humidity and temperature in a circle anaesthe}c system” November 2002
[59] D.Chiumello et al. „Effect of body mass index in acute respiratory distress syndrome” 01 Jan 2016
[60] C.Anger et al. „[Characteris}cs of the rela}ve humidity and temperature in the inspiratory part of the Dr. ger circle system and their influence on the func}on of the ciliary epithelium]” February 1990
[61] G.I. Bardoczky et al. „Large }dal volume ven}la}on does not improve oxygena}on in morbidly
obese pa}ents during anesthesia” August 1995
[62] J.I.M. Blanco „An}histamines and azithromycin as a treatment for COVID-19 on primary health care – A retrospec}ve observa}onal study in elderly pa}ents” April 2021
[63] L.R.Reznikov et al "Iden}fica}on of an}viral an}histamines for COVID-19 repurposing” 29 Jan 2021
[64] M.Urb et al. „The Role of Mast Cells in the Defence against Pathogens” 26 April 2012
[65] D.Ragab et al. „The COVID-19 Cytokine Storm; What We Know So Far” 16 June 2020
[66] W.J. Schnedl et al. „Diamine oxidase supplementa}on improves symptoms in pa}ents with histamine intolerance” December 2019
[67] G.M. Calder.n et al. „Effects of Toxin A from Clostridium difficile on Mast Cell Ac}va}on and Survival” Jun 1998
[68] R. Malaviya, et al. „Mast cell modula}on of neutrophil influx and bacterial clearance at sites of
infec}on through TNF-alpha”. Nature. 1996;381:77–79.