The aspirin triad

The term "aspirin triad" is used to describe a type of bronchial asthma that is complemented by intolerance to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs, as well as polyposis rhinosinusopathy (or nasal polyposis). The bronchial asthma proper can occur in atopic and non-atopic forms, but the signs of the aspirin triad are usually unchanged - they are signs of asthma combined with polyposis growth in the nose and/or sinuses. [1]

Epidemiology

The aspirin triad is a chronic inflammatory process involving the respiratory system. Many structures are involved in this process - in particular, mast cells, eosinophils, t-lymphocytes. Under a certain set of unfavorable circumstances, the disease causes patients repeated attacks of wheezing, difficulty breathing, a feeling of pressure in the chest, coughing - especially at night or in the morning. This symptomatology is manifested against the background of variable obstruction of the bronchial trunk, which can be reversible to varying degrees (disappears by itself or as a result of treatment).

Aspirin asthma is spoken about when it is necessary to give a clinical and pathogenetic characterization of the disease, if one of the provoking factors are non-steroidal anti-inflammatory drugs - in particular, aspirin. The pathology is manifested by a triad of clinical signs:

• polyposis rhinosinusitis;
• a seizure-like shortness of breath;
• lack of tolerance to non-steroidal anti-inflammatory drugs.

Often the pathology is combined with atopic asthma, but it can also occur separately.

There is no clear evidence of genetic predisposition to the aspirin triad. But work on this issue is not complete, as there is information on some familial cases of combined bronchial asthma and acetylsalicylic acid intolerance.

The pathology develops more often in patients 30-50 years old, and more often in women. Among all cases of bronchial asthma, aspirin triad is registered in 9-20% of patients (according to the latest statistical information - in 38-40% of patients). Of these, in 2-10% of patients with moderate asthma, and in 20% of patients with severe asthma.

Acetylsalicylic acid found its clinical application in 1899: the drug was used as an analgesic and antipyretic. Four years after its debut, the first aspirin allergic reaction was described, which was accompanied by laryngospasm and the development of shock. Two years later, doctors reported several more cases of dyspnea due to aspirin.

In 1919, a correlation between hypersensitivity to acetylsalicylic acid and the occurrence of polyposis rhinosinusitis was discovered. Three years later, bronchial asthma also joined these factors: thus, a symptom complex was "born", which was called by the term "aspirin triad". The pathology began to be studied more thoroughly, focusing on the etiology, clinical picture, and pathophysiological features of the disorder.

Overall, the aspirin triad is diagnosed in approximately 0.3-0.9% of the world's population. Many scientists point to the relatively infrequent incidence in pediatric patients. However, most pediatricians agree that aspirin triad develops frequently in children but is rarely diagnosed.

Causes of the aspirin triad

Aspirin triad refers to one of the variants of intolerance to non-steroidal anti-inflammatory drugs, since they can provoke narrowing of the bronchial lumen. Acetylsalicylic acid, better known as "aspirin", is the most frequent "provocateur" of the pathology.

The aspirin triad is referred to in medical circles as the Fernand-Vidal triad. This disease consists in the combined, sequential occurrence of three pathologies: polyposis rhinosinusitis, bronchial asthma with choking attacks and hypertrophic reaction to the intake of non-steroidal anti-inflammatory drugs. Basically, the essence of the disorder lies in anaphylactoid sensitivity to such medications. In childhood, aspirin asthma is always accompanied by the growth of polyps in the nasal cavity.

Acetylsalicylic acid has firmly entered the list of the most accessible and widespread medicines, which are available in almost every home. At the first signs of colds, headaches, etc., most people take a familiar pill without hesitation, without delving into the pharmacological specifics of this drug. But it has a fairly wide list of side effects, and among the possible complications are allergic reactions and aspirin triad.

The beginning of the development of pathology is associated with the intake of medications that contain aspirin. Such drugs are taken mainly when the body temperature rises, at the first signs of influenza, acute respiratory disease, as well as colds, headaches.

Acetylsalicylic acid when ingested into the human body, contributes to the destruction of cell membranes, disrupts the metabolism of fatty acids, upset water-salt balance, increases the level of ammonia in serum. However, all the mechanisms of the drug's effect on the respiratory system have not been fully investigated. Therefore, modern scientists base the causes of the disease on only two theories.

One theory points to the emergence of hypersensitivity to aspirin due to the disorder of metabolic processes with arachidonic acid, which takes part in triggering the inflammatory process. Acetylsalicylic acid inhibits the mechanism of cyclooxygenase formation, inhibits the metabolic reaction with arachidonic acid and activates other mechanisms of inflammatory reaction development. Significantly increases the level of leukotrienes, provoking edema in tissues and spasm of the bronchial lumen.

The second theory draws a parallel between the intake of non-steroidal anti-inflammatory drugs and the imbalance of prostaglandins - in particular, the pathological process leads to an increase in the level of prostaglandin F, which causes bronchial spasm associated with an attack of breathing difficulties. Some groups of scientists explain excessive accumulation of prostaglandins by genetic predisposition.

In addition, the natural form of acetylsalicylic acid is present in certain foods, the regular consumption of which can cause the symptoms of the aspirin triad. Such foods include cherries, pineapple, grapes, peaches, grapefruit, green apples, spinach, sorrel, etc. High levels of salicylates are also found in sesame oil, coconut oil, olive oil, asparagus and mushrooms.

Such medications can trigger the development of the aspirin triad:

• acetylsalicylic acid, as well as preparations containing it (Citramon, Upsarin Upsa, Ascophen, Copacil, Pharmadol, Citropak, Exedrine);
• Diclofenac;
• Ketorolac, Ketoprofen;
• Indomethacin, Ibuprofen;
• Orthofen;
• Meloxicam;
• Lornoxicam;
• Nimesulide;
• Phenylbutazone.

In addition to the above, it is recommended to cautiously carry out treatment with tablets that have a yellow-colored shell. The composition of such a shell may be represented by the substance tartazine, which can cause exacerbations of aspirin triad. [2]

Risk factors

Aspirin triad can develop due to hypersensitivity of the body to irritants. The role of such irritants can be internal or external factors. The main one is a hereditary predisposition, in the presence of which a person is recommended to pay special attention to the prevention of the disease. The presence among relatives of a patient with atypical disease is considered a hereditary factor of predisposition to the occurrence of hypersensitivities and allergic processes in the body. Despite the fact that to date, no genetic marker has yet been identified that predicts the likelihood of aspirin triad development, several types of "high-risk" genes have been verified. [3]

The most common external factors become frequent infections of the respiratory system, allergic processes. Thus, the development of aspirin triad can stimulate:

• medications (non-steroidal anti-inflammatory drugs - in particular acetylsalicylic acid);
• frequent psycho-emotional outbursts, stress;
• Potential allergens (food, fungal quarrels, pet hair, dust and pollen, chemicals, etc.);
• cigarette smoke (meaning both active and passive smoking), cosmetics, aerosols;
• bacterial and viral infections;
• excessive physical overload;
• hepatic insufficiency (the factor is caused by insufficient mechanism of deactivation of inflammatory and allergic mediators);
• smoking by a woman during pregnancy, allergic reactions during pregnancy;
• Lack of breastfeeding, improper infant nutrition;
• unfavorable environmental conditions, occupational hazards;
• disorders of hormonal balance, glucocorticoid deficiency, predominance of mineralocorticoids, hyperplasia of lymphoid tissue.

Genetic predisposition can influence in the following ways:

• If at least one of the parents suffers from aspirin triad, the risk of the child developing it is 20 to 40%;
• If one relative suffers from the aspirin triad, a person has an estimated 30% chance of getting the disease;
• If the incidence of the disease among relatives is not traced, the probability of getting aspirin triad is about 10%.

Pathogenesis

At the moment, scientists are at the stage of researching all available theories that could explain the origin of the aspirin triad, as well as the mechanism of development of hypersensitivity to salicylates in general.

Bronchoconstrictor property of aspirin is caused by deactivation of cyclooxygenase enzyme, which entails excessive production of leukotrienes and development of bronchial spasm. Such reactions have much in common with allergic processes, occurring in the form of bronchial asthma, urticaria, angioedema. But nevertheless, in patients with detected allergic or immune diseases, with a prescribed history of intolerance to non-steroidal anti-inflammatory drugs, there is no evidence of the presence of specific antibodies to aspirin. The marked sensitization to allergens found in patients with the aspirin triad with nasal polyps and hyperresponsiveness to nonsteroidal drugs usually disappears. Every third patient has such background pathologies as chronic dermatitis, any type of allergy (drug, food, contact, etc.) in the medical history. This is probably due to the location of the LtC4-synthase gene (the final enzyme of cysteine LT production) in the 5g chromosome, very close to the IL-3, 4 and 5 genes. These genes have a leading role in the activation of the allergic process.

A typical morphologic sign of aspirin triad is increased expression of mRNA, mast cell content, and eosinophils in bronchoalveolar lavage. In bronchial biopsy material obtained in aspirin triad, the presence of eosinophils was four times greater than in patients with bronchial asthma with adequate drug sensitivity.

The information on the expression of cyclooxygenase 1 and 2 in bronchial flush and biopsy biomaterial in different patients is rather unstable. Thus, the expression of LtC4-synthase enzyme in biomaterial was recorded 5 times higher in aspirin triad compared to patients with classical bronchial asthma (and almost 20 times higher than normal in a healthy person). In addition, the majority of aspirin-sensitive people had high initial content of LTE4 and LTC4 in urinary fluid and nasal lavage (up to 10 times higher than in other patients). Nevertheless, against the background of a severe attack of classical bronchial asthma, an increase in the level of LTE4 in urinary fluid has been observed in patients of all ages. And not all patients suffering from bronchial asthma demonstrate increased LtC4 content in nasal fluid. Similar metabolic shifts are found in relatively healthy people without hypersensitivity to salicylates. For the appearance of characteristic pathological signs it is necessary to influence other factors (we can talk about a disorder of the functional ability of the liver).

The pharmacologic abilities or biological transformations of acetylsalicylic acid were not altered in patients suffering from aspirin triad. Basically, pathologic symptomatology could also occur during treatment with non-steroidal anti-inflammatory drugs having a different chemical structure.

Despite the fact that the pathogenetic features of aspirin triad development are not fully disclosed, at the moment the most plausible theory is considered to be the inhibition of cyclooxygenase enzyme by medications, with further accumulation of sulfide-peptide leukotrienes in the respiratory system, provoking the development of obstruction.

There is no striking evidence for a genetic mode of transmission, although descriptions of familial cases of aspirin triad are available.

Symptoms of the aspirin triad

Aspirin triad is often preceded by a chronic form of rhinitis, capable of exacerbation against the background of acetylsalicylic acid intake. Such rhinitis appears, as a rule, in patients 20-40 years old. After a while, nasal polyps are detected, hypertrophic and purulent inflammatory processes develop in the sinuses, eosinophilia and the clinical picture of bronchial asthma are noted. Standardly, the triad includes:

• a hypersensitivity reaction to aspirin;
• nasal polyps;
• bronchial asthma.

If rhinitis, sinusitis and polyposis are absent, then aspirin bronchial asthma is considered. One in two patients has positive skin tests with various allergens, but asthmatic episodes occur predominantly due to non-immune exposures.

Asthmatic episodes can be quite severe, accompanied by swelling of mucous tissues, conjunctivitis and the appearance of massive nasal discharge. In some patients, fainting states are noted. During an attack, it is important to timely provide the patient with emergency medical care, including the administration of corticosteroid parenteral drugs.

The main symptoms in aspirin triad may be as follows:

• Difficulty choking (severe, moderate);
• signs of nasal polyposis, rhinosinusitis, inflammatory process in the nasal cavity;
• lack of tolerance, hypersensitivity to non-steroidal anti-inflammatory drugs;
• signs of acute respiratory viral infection, influenza, allergic reactions (after 60-120 minutes from the moment of taking the medicine);
• wheezing or wheezing exhalation due to the development of bronchial obstruction;
• redness, swelling of the skin on the face and upper half of the torso, itching.

The clinical picture may take an average of three days to manifest, and in general from 12 hours to three weeks.

Nasal polyposis can be asymptomatic. When large or numerous polyps form, nasal passages may be blocked, nasal breathing problems may occur, the sense of smell may be lost, and infectious and inflammatory processes may become more frequent. Nasal polyposis is directly related to the appearance of chronic inflammation of the nasal mucosa or sinuses. However, sometimes chronic sinusitis occurs without the formation of polyps.

The usual "classic" symptoms of chronic rhinosinusitis and polyposis are:

• persistent nasal discharge (systematic, or year-round runny nose);
• persistent nasal congestion;
• Postnasal congestion (secretions run down the posterior surface of the pharyngeal wall);
• diminished or lost sense of smell;
• insufficient taste sensation of food or complete loss of taste sensation;
• facial pain with irradiation to the upper jaw;
• frequent headaches;
• pressure sensation in the frontal, facial area;
• the onset of snoring.

The symptomatology of polyposis and rhinosinusitis can not be called specific, but the combination of signs along with the picture of bronchial asthma and hyperreaction to the administration of salicylates helps to suspect the development of aspirin triad in the patient.

These symptoms require urgent medical intervention:

• a choking attack, severe respiratory distress;
• a sharp deterioration of well-being;
• diplopia, narrowing of the visual field;
• increasing swelling of the skin and mucous membranes;
• A sudden increase in headache in which the patient is unable to tilt the head forward.

First signs

As a rule, aspirin triad begins with the appearance of vasomotor rhinitis (rhinosinusitis), lasting for several months and even years. At the initial stage of the disease in the nasal secretions of patients are found a large number of eosinophils, and with a prolonged pathology (from several months to several years) in the nasal cavity are formed polyps. Against the background of polyposis development, the number of eosinophils decreases approximately twofold, but signs of bronchial asthma and hypersensitivity to nonsteroidal anti-inflammatory drugs are added.

The clinical picture in the aspirin triad is practically the same in patients of different ages. But in children it is important to initially exclude cystic fibrosis and primary ciliary dyskinesia (Kartagener's syndrome).

Nasal congestion, runny nose, impaired olfactory function and sneezing are considered to be the most characteristic initial signs - these symptoms are found first in about 90% of patients with aspirin triad. Localized sinus pain is less frequently reported.

The first signs of acetylsalicylic acid intolerance appear:

• skin symptoms (photoallergies, exanthema, urethral rash, vasculitis in the form of pigmented purpura or erythema nodosum);
• systemic reactions (anaphylaxis);
• symptoms of the respiratory system (choking, nasal discharge, nasal and bronchial breathing difficulties, etc.);
• symptoms from the digestive system (nausea, abdominal pain, vomiting, sometimes - elevated body temperature).

Most patients with aspirin triad develop an attack of bronchospasm within the first 1-4 hours of taking acetylsalicylic acid. The face and eyes become red, there is profuse nasal discharge and periorbital edema. Episodes of attacks become more frequent over time. Further reaction to the reception of salicylates can be life-threatening for the patient: anaphylaxis develops, asthmatic status ends with a fatal outcome. Bronchial asthma progresses, becomes severe, which indicates the need for treatment with systemic glucocorticosteroid drugs.

Symptomatology from the skin and digestive tract occurs somewhat later - from 6 to 48 hours from the time of administration of non-steroidal anti-inflammatory drugs.

Stages

In medicine, such stages of aspirin triad development are distinguished:

• Intermittent stage - occurs once a week or less frequently during the daytime, and no more than twice a month at night;
• Mild persistent stage - the disease occurs during the day with a frequency of 2-3 times a week, and at night - more than twice a week;
• medium persistent stage the disease bothers every day, exacerbations occur with physical exertion, and nocturnal attacks occur 1-2 times a week;
• severe persistent stage - characterized by regularity, exacerbations even against the background of minor physical activity, frequent occurrence at night.

The division of the period of disease development into stages predetermines the specifics of treatment and patient care. This division may be considered arbitrary, but it may be of value in determining the scope of care.

Forms

Depending on the clinical course, aspirin triad is categorized into two types:

• initial pathology;
• acute aspirin triad.

The initial pathology is not accompanied by disorders of the respiratory organs and is often manifested by functional malfunctions of the endocrine system and immunity. Every sixth patient has diseases affecting the thyroid gland. Most patients complain of weakened immunity, frequent infections. The appearance of neurological signs is possible:

• Over-emotional reactions to stressful situations;
• a sense of inner restlessness and tension;
• constant unmotivated anxiety;
• sluggish depression.

Over time, pathological signs from the respiratory organs develop, rhinitis or rhinosinusitis appears, untreatable.

The acute period of aspirin triad starts with the onset of attack-like episodes of suffocation, bronchospastic states. The attack may be aggravated by such irritating factors as a sudden change in temperature, physical activity, the appearance of unpleasant odors, etc. Asphyxiation in aspirin triad differs from the classic asthmatic attack. For an hour after taking a non-steroidal anti-inflammatory drug or salicylate-based preparations, the patient has difficulty breathing and other signs:

• copious nasal mucus discharge;
• lacrimation;
• redness of the face and upper half of the torso.

Additional, but not mandatory, symptoms may include:

• lowering blood pressure;
• hypersecretion of the salivary glands;
• nausea with vomiting;
• epigastric pain.

Aspirin attack can occur regardless of the season, eventually transforming into a constant feeling of discomfort and congestion behind the sternum. The use of bronchodilators does not lead to improvement.

Complications and consequences

Patients with aspirin triad are often patients of intensive care units, where they are admitted when complications of the disease develop. Pathology is also dangerous for a long differential diagnosis. Slow diagnosis and lack of necessary treatment contribute to the aggravation of pathology and can even lead to death.

The inability to predict an attack and the patient's promiscuity in taking medication are particularly serious threats.

Complications can occur with a prolonged course of aspirin triad and inadequate treatment of the disease: pathological processes negatively affect many systems and organs of the patient.

In general, there is a risk of developing these adverse effects:

• bronchial obstruction;
• asthmatic status;
• failure of respiratory function;
• Spontaneous pneumothorax;
• atelectasis;
• Pneumosclerosis;
• pulmonary emphysema;
• pulmonary heart;
• increased blood pressure.

During an attack the patient's blood pressure invariably rises, and spastic coughing episodes provoke an increase in intra-abdominal pressure, which in combination can lead to the development of internal bleeding, fecal and urinary incontinence and so on.

In turn, nasal polyposis interferes not only with nasal breathing but also with the outflow of nasal secretions. This will cause complications such as:

• obstructive sleep apnea with interruption of breathing during sleep;
• exacerbation of bronchial asthma;
• increased sensitivity to infectious agents.

Diagnostics of the aspirin triad

The diagnosis of aspirin triad is established based on the information obtained during the collection of anamnesis, assessment of the clinical picture, etc. However, the fact of intolerance to nonsteroidal anti-inflammatory drugs is not always possible to determine during a routine interview, and nasal polyposis in the absence of additional specific signs of aspirin triad can not be the basis for the diagnosis. Therefore, diagnosis is carried out in an expanded scope, using the necessary laboratory and instrumental studies.

The disease is characterized by eosinophilia, the presence of eosinophils in nasal mucus, and impaired glucose tolerance. Positive provocation tests with methacholine and histamine are often noted. Radiographs of the appendicular sinuses demonstrate hypertrophic changes in the mucosal tissues and the presence of polyposis. Skin test with aspirin-polylysine is undesirable due to the high risk of anaphylactic reaction. The only recommended diagnostic method for determining intolerance to salicylates is considered a provocation test. However, even this method is not used for diagnosis in patients with bronchial asthma requiring continuous treatment with corticosteroids, as well as in the presence of nasal polyposis.

Interviewing a patient by a physician involves obtaining the following information:

• the possibility of hereditary predisposition;
• identifying the relationship between environmental stimuli and the development of pathology;
• the patient's reactions to foods and medications from different drug groups;
• the seasonality of the disease, the likelihood of its association with infections, long-distance travel, etc;
• the patient's other medical conditions;
• living conditions and professional activities;
• nutritional traits and preferences;
• previous laboratory diagnostics and their results;
• the effectiveness of anti-allergy medications for allergy symptoms.

An important point for the diagnosis of aspirin triad is information about the patient's body response to taking analgesics or antipyretics. Individual patients can clearly indicate the development of edema and difficulty breathing after the use of nonsteroidal anti-inflammatory drugs. If the patient does not say anything about signs of intolerance to medications, it may be a consequence:

• mild hypersensitivity;
• simultaneous use of drugs that neutralize bronchoconstrictor property of anti-inflammatory drugs (such drugs can be anti-allergic, sympathomimetic agents, theophylline);
• the body's delayed response to medication.

Episodes of the disease can also be provoked by non-drug stimuli, such as ingestion of food containing salicylates. In addition, not all patients are aware that acetylsalicylic acid is part of other medicines - in particular, Citramon, Ascophen, Baralgin, Thrombo Ass and so on. The intensity of the body's reaction depends greatly on the dosage of the drug, and on the method of its administration. Thus, inhalation, intravenous and intramuscular administration usually causes the most pronounced reaction.

The interview is followed by an examination: the doctor focuses on the condition of the skin and mucous membranes, the quality of breathing. Feel and evaluate the condition of the lymph nodes.

Laboratory investigations include general clinical tests:

• blood and urinalysis;
• blood chemistry;
• cytologic and bacteriologic analysis of nasal discharge;
• Examination of sputum (if present);
• virologic, parasitologic diagnostics;
• rheumatic tests;
• hormonal studies.

In order to definitively confirm the diagnosis of aspirin triad, in vivo or in vitro provocation testing is currently used. The first option involves oral administration of aspirin, or inhalation with increasing concentrations of aspisol, with further observation of bronchial patency. Due to the high risks of obstruction, testing should only be performed by an experienced physician under all necessary conditions. Since anti-allergic drugs desensitize the patient to the test, they should be withdrawn at least 2 days before the diagnosis. Theophylline, sympathomimetics and other similar drugs are also discontinued at least one day in advance.

Currently, scientists are working on the possibility of diagnosing the aspirin triad by detecting leukotrienes E4 in urine and C4 in nasal mucus. When performing provocative testing with aspisol in patients with hypersensitivity to salicylates, there is a dramatic increase in leukotriene E4 levels in urine and C4 levels in nasal secretions.

Instrumental diagnosis involves the assessment of external respiratory function. Spirometry is performed according to the following indicators:

• PEF1 is a measurement of forced expiratory volume in 1 second;
• FGEF - measurement of forced vital capacity of the lung;
• Ind. Tiffno - measuring the ratio of the above two indicators;
• PSV is a measurement of peak expiratory flow rate;
• MOS is a measurement of the limiting expiratory flow rate at the level of bronchi of different caliber.

If there is an obstruction, it is determined by lowering of EFV less than 80% of normal, lowering of Tiffno index.

The reversibility of obstruction is checked by bronchomotor testing (using β-antagonists).

Other diagnostic methods used may be:

• CT or chest x-ray (ordered to differentiate or identify deformities of the sternum and spinal column); [4]
• X-ray of the sinuses (to detect rhinosinusitis, polyposis);
• electrocardiogram (to determine background heart disease);
• bronchoscopy (for differential diagnosis with other diseases of the respiratory system).

In the course of histological examination of polyposis formations in patients with aspirin triad, typical manifestations of the allergic inflammatory process are found, which proceeds according to the mechanism of hypersensitivity of immediate type (severe edema, eosinophilic infiltration, exudative-vascular reactions, etc.) or delayed type (follicular accumulation, infiltration with lymphocytes, macrophages, neutrophils, etc.).

Differential diagnosis

A differential diagnosis should be made:

• with atopic bronchial asthma;
• with chronic pulmonary obstruction;
• with acute respiratory infections;
• with tuberculosis and tumor process;
• with cardiac asthma.

Treatment of the aspirin triad

Treatment of the aspirin triad is based on the following principles:

• controlling the symptomatology of the disease;
• Compliance with measures to prevent (prevent) exacerbations, in particular - the appearance of attacks of suffocation;
• maintaining normal respiratory function;
• Ensuring adequate life activity of the patient;
• elimination of unfavorable provoking medication and nutritional factors;
• prevention of irreversible obstruction of the respiratory tract;
• Avoiding death from respiratory obstruction.

Patients need to follow such strict rules:

• to adjust the diet, to bring it closer to the natural diet;
• completely exclude products with salicylates, as well as medicines that can provoke an exacerbation of the disease (Aspirin, Baralgin, Spasmalgon, Diclofenac, Indomethacin, etc.);
• systematically visit a doctor for preventive diagnostics.

Nutritional correction is of great importance in the treatment and prevention of aspirin triad. First of all, it is necessary to exclude from the diet all foods containing salicylates.

A list of foods that are forbidden to eat:

• roasted or smoked meats;
• marinades and canned foods with acetylsalicylic acid;
• gelatin, jelly, etc;
• store-bought sauces, preservative-laden products;
• industrial baking;
• starchy foods;
• sodas, sugary waters, packaged juices;
• med;
• alcoholic beverages.

It is recommended to consume fish, seafood, vegetable oil, green tea, coffee, natural milk and sour milk products (without additives), homemade bread.

In the treatment of aspirin triad, a stepwise approach is used, and the intensity of therapy is increased as the severity of the disease increases. Inhaled corticosteroids, cromoglycate or nedocromil sodium, prolonged theophylline and sympathomimetics are often the basic drugs of choice. [5]

Often systemic steroid medications have to be used as well.

A common method of treatment of patients with aspirin triad is aspirin desentitization. The technique is based on the formation of the body's tolerance to repeated exposure to the drug in a limited term - within 1-3 days after a suffocating attack provoked by taking a non-steroidal anti-inflammatory drug. Studies have shown that such desensitization allows you to control the clinical picture of rhinosinusitis and bronchial asthma: treatment is carried out according to an individually designed scheme, only in inpatient conditions and under the supervision of the attending doctor. As a rule, the initial dosage is no more than 5-10 mg, gradually it is brought up to 650 mg and more. Desensitization is not prescribed:

• during the period of exacerbation of the disease;
• if you're prone to bleeding;
• for peptic ulcer disease;
• in severe kidney and liver pathologies;
• when you're pregnant.

Specialists point out that the method is due to the development of insensitivity of airway receptors to the action of leukotrienes.

Today, a new group of antiasthmatic agents - leukotriene receptor antagonists - is increasingly being mentioned. These drugs relieve the basal tone of the respiratory tract, which is created by leukotrienes with constant stimulation of the 5-lipoxygenase enzyme system. Zafirlukast (Acolate) can be called a striking representative of such drugs. When administered orally, this drug causes a marked increase in EFV1 (forced expiratory volume) in patients with respiratory dysfunction who have previously taken antiasthmatic and corticosteroid drugs.

If there is a need for pain relief or lowering the temperature, then the patient instead of non-steroidal anti-inflammatory drugs is allowed to take Paracetamol, starting from 500 mg. But even in this case, it is important to monitor the condition of the body, because in about 5% of cases, even this medicine can provoke an attack.

Medications

Aspirin triad patients should beware of taking medications that contain acetylsalicylic acid and other non-steroidal anti-inflammatory drugs. The doctor necessarily explains to patients that before using any drug it is important to carefully read the instructions and the composition of the medication, to make sure that there are no components in it that can provoke an attack of the disease. A sick person should know all the existing names of aspirin, as well as the names of other potentially dangerous drugs.

It is known that the coloring substance tartrazine, which is part of the yellow tablet shell and some foods, can have an undesirable provoking effect in every second aspirin triad patient. Therefore, to avoid recurrences, the doctor may recommend avoiding the use of medications and foods that have a yellow-orange color.

The aspirin triad often requires treatment with inhaled and systemic corticosteroids as well as other medications:

• Medications to prevent the development of recurrent seizures:
  • Inhaled steroid medications;
  • systemic steroids (if inhaled agents are ineffective);
  • inhaled medications that dilate the bronchial lumen;
  • leukotriene receptor antagonists.
• Medications for emergency medical care (in case of disease exacerbation, suffocation attacks):
  • Bronchodilators, fast-acting β2-adrenomimetics;
  • oral corticosteroids;
  • oxygen therapy;
  • adrenaline (for severe attacks).

If it is necessary to prescribe glucocorticosteroids, preference is given to Methylprednisolone and Dexamethasone, since there is information about the development of bronchospasm with intravenous administration of Prednisolone and Solu-Cortef (hydrocortisone). It is advisable to use antileukotriene agents, which can reduce the intensity of the clinical picture of the disease and even reduce the dosage of systemic glucocorticosteroids. Such agents are most often represented by Zafirlukast or Monterlukast, which have similar clinical efficacy and perfectly complement the main antiasthmatic treatment. These drugs are well tolerated when taken orally, rarely cause side effects (dyspepsia, headache, increase in serum transaminases), have virtually no sedative effect:

• Acolate (Zafirlukast) is started at 20 mg twice daily, between meals;
• Singulair (Monterlukast sodium) is taken 10 mg (1 tablet) daily before going to bed.

Antihistamines in aspirin triad are usually H1-histamine receptor blockers, which reduce the release of mediators from basophils and mast cells:

• Cetirizine is taken at 10 mg per day;
• Ebastine is taken at 10 mg per day, with a maximum daily dosage of 20 mg;
• Fexofenadine is taken 120-180 mg daily;
• Loratadine is taken at 10 mg per day.

Antihistamine treatment may be accompanied by sedative and sleeping effect of drugs, as well as their cholinolytic activity (dry mucous membranes, palpitations, constipation, oliguria, increased sputum viscosity).

A combination of antihistamines and vasoconstrictors is often practiced - for example, Clarinase (a combination of 5 mg loratidine and 120 mg pseudoephedrine). The drug is prescribed 1 tablet twice a day.

Non-hormonal and hormonal agents are administered intranasally: Cromoglycate sodium (Cromohexal, Cromoglin, Lomuzol), Acelastin (Allergodil), Levocabastin (Histimet). Cromoglycate sodium is used 4 times a day, and nasal sprays are used 1-2 times a day.

Topical hormonal agents can be used in the form of Aldecin, which can be administered either inhaled or intranasally. Nasonex has an excellent anti-inflammatory effect: two doses (100 mcg) into each nasal passage daily in the morning.

Antibacterial treatment is not one of the main methods, but it is often prescribed for proven infectious inflammation of the respiratory organs. The preferred antibiotics are macrolides (Azithromycin, Spiramycin) and fluoroquinolones (Ofloxacin, Norfloxacin, etc.). The duration of antibiotic therapy is usually limited to 5-7 days.

Physiotherapeutic treatment

The issue of recovery of patients suffering from aspirin triad has always been considered very difficult, because this pathology can cause disability and even death. A stable period of remission can be achieved only thanks to adequate pathogenetic therapy, the basic direction of which is to ensure control of the pathology. Special measures are supplemented by resort treatment, aimed at eliminating or reducing the intensity of the clinical picture, restoration or optimization of disturbed respiratory functions, training adaptation of the body, strengthening its resistance. Often rehabilitation complexes include climatic procedures, hydrotherapy, balneotherapy, breathing exercises, massage, manual therapy, inhaler administration of drugs (bronchodilators, minvod, herbal infusions), aerophytotherapy and so on. Spa therapy affects the different pathogenetic links of the disease, helping to achieve lasting relief and respiratory function without further progression of pathology and its transformation into more complex forms.

Treatment may be indicated for patients with aspirin triad in remission with mild or infrequent episodes if respiratory insufficiency does not exceed grade II. If the disease is in the stage of unstable remission, is hormone-dependent controlled, if there is pulmonary and cardiac insufficiency, not exceeding I degree, then treatment is allowed only near the region of residence of the patient.

Physical therapy is not prescribed:

• if the patient is asthmatic, if there are attacks at the time of the appointment;
• if you have chronic pneumonia;
• if there are indications of particularly severe attacks accompanied by cardiac distress and asphyxia.

In order not to aggravate the situation, before sending to a sanatorium-resort treatment, the patient must undergo a mandatory examination, sanitation of foci of chronic infection.

The scheme (program) of physiotherapy is made individually for each patient, based on the results of clinical examination.

Herbal treatment

Bronchodilators, expectorants and anti-allergic drugs, hormonal and antibacterial agents are often used to treat the aspirin triad. Despite the wide range of therapeutic measures, they are not able to completely rid a person of the disease, and give only temporary relief, as well as some side effects: digestive disorders, liver and kidney dysfunction, metabolic failures, etc. Therefore, more and more often patients resort to the help of phytotherapy - a method that has accumulated centuries of experience of folk healers. But treatment with herbs requires caution: even medicinal plants can cause allergic reactions, so herbs should be added one by one, gradually, under the supervision of a doctor.

To improve bronchial permeability, pay attention to herbs that relieve spasms of bronchial muscles: Ledum, ivy-leaved buddleia, beechberry, thyme and celandine, angelica, cowslip, celandine, etc. To reduce the intensity of edema of mucous tissue in the medicinal mixture include elecampane, aira rhizome, horse chestnut, St. John's wort, lapwort, rosehip, common cuff. Supplement the mixture with herbs with expectorant effect, which include plantain, licorice, althea, mother and stepmother.

Herbal mixtures are taken in the form of an infusion, for the preparation of which the raw materials are poured very hot water (about 90 ° C), insist under a lid for about 1 hour and drink in three doses half an hour before meals. It is better to drink the remedy in warm form, since the infusion from the refrigerator can provoke an attack of bronchospasm, regardless of the likelihood of allergens in the body.

A good effect has a good lotion on the chest area with an infusion of breast or anti-asthmatic collection. The procedure is carried out before bedtime, the chest is wrapped with a warm scarf or towel. The action of this method is based on the active absorption of useful and therapeutic substances through the skin.

Treatment with herbs also involves the preparation of herbal ointments. They are prepared from a dry herbal mixture, which is ground to a powdery state and mixed with internal pork fat. Such ointment can be used in a complex: to rub the chest, to lubricate the mucous membrane of the nasal cavity.

Phytotherapy is usually well tolerated by almost all patients with aspirin triad. However, it is important to note that such patients should exclude the use of herbal products and herbs that contain salicylates. We are talking about meadow clover, willow, willow, meadowsweet, chamomile, black currant, apple leaves and fruits, sorrel and rhubarb, spinach.

The most recommended plants for phytotherapy for aspirin triad:

• Thyme in the form of aqueous infusion is characterized by expectorant, antiseptic, bronchodilating properties. The plant loosens viscous phlegm, helps to cough it up sooner, and also relaxes the smooth bronchial muscles. To prepare an infusion of 1 tbsp. Dry thyme insist for 60 minutes in a closed kettle in 250 ml of hot water. After filtration, the infusion is taken one sip three times a day.
• Licorice (root) is known for its strong anti-inflammatory, antispasmodic and mucolytic action, as well as moderate anti-allergic properties. This herb is included in most anti-asthmatic collections. With aspirin triad take 15 g of crushed rhizome, pour 400 ml of boiling water in a thermos, insist for half an hour. After filtration, take one sip of the remedy three times a day between meals.
• Pine buds have expectorant, antibacterial and anti-inflammatory properties. Kidneys in an amount of 10 g pour 250 ml of boiling water in a thermos, kept for two hours, filtered. Take the remedy 2 tbsp. 4 times a day.
• Leaves and flowers of mother and stepmother have an enveloping, mucolytic and anti-inflammatory effect due to the presence of essential oils, glycosides and saponins in the plant. Pour 15 g of raw materials 250 ml of hot water. Infused, filtered. Drink warm one small sip 6 times a day.
• Devyasil has expectorant, anti-inflammatory, anti-allergic and sedative properties. The roots of the plant are crushed, pour 2 tsp. Raw materials 500 ml of hot water, kept overnight (about 8 hours). Filter, drink 100 ml 4 times a day half an hour before meals.
• Leaves of primrose are an excellent antispasmodic and mucolytic agent. To prepare the drug, 5 g of dry raw materials are crushed to a powdery state, pour 200 ml of hot water, insist until cooled, filtered. Take the remedy 50-100 ml three times a day.

In addition, prepare medicinal collections, which include anise seeds, leaves of sage, mint and plantain, grass tricolor violet and St. John's wort, rhizome of valerian and bilberry, as well as motherwort, thyme, saplings of gray alder.

Surgical treatment

There is not only medication, but also surgical treatment of aspirin triad, and more specifically, polyposis rhinosinusitis.

If conservative treatment of rhinosinusitis and nasal polyps proves ineffective, the patient is prescribed surgery. The intervention does not lead to an exacerbation of bronchial asthma and significantly improves the patient's condition.

Modern surgery for this purpose applies endoscopic methods, using special optical devices. Thanks to this, it is possible to remove only the pathologically altered part of the mucosa, as well as to eliminate the anatomical prerequisites for the development and re-growth of polyps. In particular, it is possible to correct the nasal septum, expand the mouths of the sinuses, eliminate additive openings, and so on. The recurrence of polyposis after a competently performed intervention is rare.

Diffuse polyposis rhinosinusitis usually requires conservative treatment, such as topical or internal administration of hormonal corticosteroid drugs. Corticosteroids have a strong anti-inflammatory effect, inhibit polyp enlargement and prolong the remission period of the aspirin triad. Treatment courses are usually long - often for life. Treatment can be supplemented with other groups of drugs - for example, antibiotics. If the patient is prescribed surgery, its main purpose is the complete removal of nasal polyps, correction of defects - not only to improve respiratory function, but also to facilitate the entry of local drugs into the sinuses.

What surgeons warn their patients about:

• Aspirin triad is a chronic and recurrent pathology of an incurable nature. Therefore, the basic task of the doctor is to prescribe a complex therapy that helps to maximize the asymptomatic course of the disease and relieve the patient's well-being.
• Some patients may require repeat surgeries, and multiple surgeries at that.
• Even after surgical intervention, patients should be systematically monitored by a physician, and topical hormonal agents should be used daily - often for life.
• It is important to properly manage the postoperative period, in accordance with the doctor's recommendations. Otherwise, the effect of the surgery may be offset.

Most often, surgeons use functional endoscopic rhinosinus surgery for patients with aspirin triad. This is a modern nasal surgery where the intervention is performed without incisions, but only through the nose. A nasal endoscope is placed in the nasal passage. Thanks to an illuminating device and four times optical magnification, the doctor during the operation can see all the intracavitary (intranasal) structures, as well as the sinuses. This procedure is technically uncomplicated and effective at the same time. [6]

Prevention

Preventive measures are primary and secondary.

Primary prevention of aspirin triad is aimed at preventing the appearance of pathology. Secondary prevention involves complex measures, the purpose of which is to improve the patient's condition, to prevent the development of an acute episode of the disease and the emergence of complications in advance. The primary type of prevention is recommended as mandatory actions for people at risk of aspirin triad. Such a risk group includes:

• persons with an aggravated family history (if there have been previous cases of such pathology in the family);
• patients with secondary croup development;
• people who are prone to allergic reactions;
• patients with signs of atopic dermatitis;
• people whose occupations may contribute to respiratory problems (prolonged stay in dusty rooms, work with chemicals, etc.);
• persons suffering from bronchoconstriction, complications of viral infections;
• smokers.

Primary prevention measures may be as follows:

• promotion of the body's immune defense, hardening procedures, regular physical activity;
• Limiting the use of household chemicals, especially in the form of sprays and aerosols;
• planning and correct management of pregnancy, contributing to the good health of the future child;
• rational diet, minimization of potentially allergenic products, correction of drinking regimen;
• correction of professional conditions;
• avoiding bad habits;
• prevention of infectious and inflammatory diseases, viral infections, prevention of chronicization of diseases;
• taking medications only as prescribed by the attending physician, avoid self-medication;
• the practice of breastfeeding your baby until he or she is 1.5-2 years old;
• Prevention of passive inhalation of cigarette smoke;
• regular walks in the fresh air, breathing exercises;
• avoiding prolonged stay in environmentally unfavorable regions, near highways and industrial enterprises.

Secondary prevention consists of the following:

• treatment of chronic pathologies of the respiratory tract, infectious diseases;
• complete elimination of contact with potential allergens;
• regular damp cleaning of the permanent area;
• frequent airing of the room, drying of bedding in the open air (including pillows and blankets);
• Getting rid of household items that tend to accumulate dust (carpeting, lint pillows and toys, etc.);
• absence of pets or indoor flowering plants in the house, if they can provoke allergies or shortness of breath;
• Getting rid of mold particles and excess moisture in the home;
• preference in the choice of pillows made of synthetic fillings (feather and down can cause a suffocation attack in allergy-prone people);
• Exclusion of foods recognized as potential allergens from the diet;
• preventing the incidence of acute respiratory diseases and viral infections;
• Careful adherence to all hygiene rules;
• Avoiding self-medication, careful and cautious use of any medication;
• maintenance of physical activity, walks in the fresh air, breathing exercises;
• Strengthening the body, supporting the immune system, avoiding bad habits.

It is also welcomed periodic resort and sanatorium vacation, timely visit to the doctor in case of any health problems.

Forecast

Despite the development of new effective drugs and therapies, the prevalence of aspirin triad cases is steadily increasing, especially in pediatrics. At the same time, treatment is mainly aimed at achieving and maintaining control of the pathology. The prognosis is considered relatively favorable, since the disease is chronic and requires constant monitoring.

The aspirin triad is characterized by recurrences of inflammatory processes, exacerbations, which are periodically manifested by coughing, difficulty breathing and other typical signs. In many patients, such relapses are quite severe and require intensive care measures. Severe exacerbations can develop in almost any patient, regardless of the severity of the disease as a whole: that is, a severe attack can occur against the background of easy aspirin triad.

Thanks to the successful work of researchers and modern pharmaceutical advances, the number of choking episodes in patients admitted to intensive care units has decreased over the past few decades. The incidence of patient deaths has also decreased. However, the number of aspirin triad patients in the world continues to grow steadily.

The main task of doctors to achieve a positive prognosis is to establish control over the pathology. Under control, specialists mean a decrease in the severity of symptoms and the disappearance of exacerbations, as well as satisfactory indicators of clinical and instrumental diagnostics.

It is possible to control the disease, and this has been proven many times: for example, positive sustained dynamics is achieved in about every second patient suffering from chronic aspirin triad. The following factors worsen the quality of prognosis:

• nicotine addiction (according to statistics, every fourth patient has such a bad habit as smoking);
• The simultaneous existence of aspirin-induced asthma and chronic pulmonary obstruction;
• Constant exposure to household or industrial allergens;
• patient's non-serious attitude to treatment, non-compliance with medical recommendations;
• viral lesions;
• overweight of the patient (different degrees of obesity);
• gastroesophageal reflux;
• Chronic and intense otorhinolaryngologic background diseases;
• hormonal disorders, imbalances caused by periods of menopause, puberty, etc..;
• psychological disorders;
• inappropriate treatment regimen.

One indicator of established disease control is a clear reduction in the frequency of night awakenings due to asthma attacks. However, some patients do not achieve such control. The efficacy of therapy is influenced by comorbidities that may impair susceptibility to treatment. The most dangerous background conditions are considered pathologies of the respiratory system, respiratory infections, obstructions, psychopathological problems, atopic dermatitis, bad habits. For example, smoking significantly hinders pulmonary performance, aggravates the course of asthma, reduces the body's response to the use of inhaled and systemic glucocorticosteroid drugs. Given the above, the prognosis in such a disease as aspirin triad should be considered only individually.