List of Abbreviations
BPD – bronchopulmonary dysplasia
ВПС – congenital heart disease
RF – respiratory failure
IMV – invasive mechanical ventilation
ICS – inhaled corticosteroids (R03BA – Corticosteroids)
RSVI – respiratory syncytial virus infection
SBP – systolic blood pressure
RR – respiratory rate
HR – heart rate
NCPAP (nCPAP) – Nasal Continuous Positive Airway Pressure – continuous positive airway pressure via nasal cannulas (non-invasive mechanical ventilation)
NIPPV – non-invasive positive pressure ventilation (non-invasive mechanical ventilation)
Terms and Definitions
New and narrowly focused professional terms are not used in these clinical guidelines
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
According to the Classification of Clinical Forms of Bronchopulmonary Diseases in Children adopted in Russia [1], acute bronchiolitis (J21) is defined as an inflammatory disease of the lower respiratory tract with predominant involvement of the small bronchi and bronchioles, developing in children under 2 years of age (most frequently in children under 1 year of age).
The symptom complex of acute bronchiolitis includes lower respiratory tract obstruction occurring against the background of an acute respiratory viral infection (или при воздействии раздражителей) and accompanied by cough and signs of respiratory failure: labored grunting respiration, tachypnea, intercostal and/or subcostal retractions, nasal flaring, and bilateral wheezing in the lungs [2,3].
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
Bronchiolitis most commonly develops as a manifestation of respiratory syncytial (RS) viral infection (60–70%). In premature infants, especially those with bronchopulmonary dysplasia (BPD) and on formula feeding, rhinovirus may be an etiologically significant agent in bronchiolitis (up to 40% of cases) [4]. Influenza A and B viruses, parainfluenza virus, adenovirus, coronavirus, metapneumovirus, and human bocavirus are also considered as causative factors of the disease.
Virtually all children contract RS viral infection in the first 2 years of life (90%), yet bronchiolitis develops in only approximately 20% of cases, which may be due to the presence of predisposing factors [5].
Additional risk factors for the development of bronchiolitis include:
Presence of older siblings in the family.
Age under 6 months.
Birth $\le$6 months before the start of the RSV season.
Large family ($\ge$4 people).
Breastfeeding $\le$2 months.
Attendance at a daycare center.
Children from multiple pregnancies [6,7,8].
Risk factors for severe bronchiolitis:
Prematurity (<35 weeks of gestation).
BPD.
Other chronic respiratory tract disorders (e.g., congenital malformations).
Hemodynamically significant cardiovascular disorders.
Immunodeficiencies.
Age under 3 months.
Male sex.
Low socio-economic status of the family.
Maternal smoking during pregnancy, passive smoking.
RS infection.
Neuromuscular diseases.
Genetic characteristics [2,3,63].
The pathogenesis is mainly driven by necrosis and desquamation of the terminal and respiratory bronchiole epithelium, lymphocytic and neutrophilic infiltration, and edema of their walls. Mucus hypersecretion is also observed.
The morphological characteristics of acute viral bronchiolitis explain the low efficacy of drugs used to treat obstructive airway diseases in the majority of patients.
Bronchiolitis may lead to the development of microatelectases in cases of complete obstruction of the lumen of affected airway regions or, in partial obstruction, diffuse manifestations of the "air trapping" sign. In turn, atelectases and "air traps" contribute to the development of hypoxemia and hypercapnia due to ventilation-perfusion mismatch.
Exhalation performed with the effort of respiratory muscles leads to symptoms of respiratory failure, especially in premature infants, children with BPD, congenital heart defects (CHD), and neuromuscular pathology [3].
In some cases (more often in newborns, especially premature infants younger than 44–48 weeks of postconceptional age and when the etiologic factor is respiratory syncytial virus), central apnea may appear at the very beginning of the disease, prior to the onset of classic symptoms of acute bronchiolitis [45].
Children with bronchiolitis may develop catarrhal otitis media, which is confirmed by otoscopy. Purulent otitis media accompanies bronchiolitis extremely rarely. Urinary tract infection is detected in 3.3%. Bacteremia – in 0.3% [9].
Secondary bacterial pneumonia occurs in less than 1% of cases [10]. The risk of secondary bacterial pneumonia increases in children hospitalized in the ICU, especially when intubated [11,12]. The incidence of bacterial co-infection in children with acute bronchiolitis hospitalized in the ICU can reach up to 31% [64].
1.3 Epidemiology of the Disease or Condition
Bronchiolitis is most common in children under 9 months of age (90% of cases). Globally, 150 million cases of bronchiolitis are registered annually (11 cases per 100 infants), 7–13% of which require inpatient treatment and 1–3% – admission to the intensive care unit [3]. According to Russian data, the incidence of bronchiolitis is 114–137 per 1,000 children [65].
The seasonal peak of bronchiolitis incidence in our geographical latitudes was previously observed from November to April; following the novel coronavirus infection (COVID-19) pandemic, seasonality is less distinct, with cases and incidence peaks occurring throughout the calendar year [60].
1.4 Features of Coding the Disease or Condition
Acute bronchiolitis (J21)
J21.0 – Acute bronchiolitis due to respiratory syncytial virus
J21.1 – Acute bronchiolitis due to human metapneumovirus
J21.8 – Acute bronchiolitis due to other specified agents
J21.9 – Acute bronchiolitis, unspecified.
B97.4 – Respiratory syncytial virus as the cause of diseases classified in other chapters
Examples of diagnosis formulation:
Acute bronchiolitis (RS viral). Respiratory failure grade II.
Acute bronchiolitis. Respiratory failure grade I.
1.5 Classification of the disease or condition
There is no unified classification of bronchiolitis.
Clear criteria for the severity of bronchiolitis have not yet been developed. To assess the severity of bronchiolitis, one should be guided by signs of respiratory failure (Table 1 and Table 2).
Table 1. Symptoms of respiratory failure in children (WHO, 2015)
Tachypnea, respiratory rate per minute: - Children 0-2 months > 60 - Children 2-12 months > 50 - Children 1-5 years > 40 - Children older than 5 years > 20 |
Dyspnea, labored breathing |
Indrawing of compliant areas of the chest during inspiration |
Grunting/moaning respiration |
Nasal flaring during breathing |
Apnea |
Impaired consciousness |
SpO2 values < 90% in room air |
Table 2. Assessment of acute respiratory failure in children
Degrees of RF | Characteristics |
|---|---|
I | Dyspnea, tachycardia, perioral cyanosis, and nasal flaring upon minimal physical exertion. SBP is normal, pO2 = 65-80 mmHg. SpO2 = 90-95% |
II | Dyspnea, tachycardia, ↑SBP, perioral, acrocyanosis, and skin pallor at rest; worsen with physical exertion. The child is agitated and restless, or lethargic. pO2 = 51-64 mmHg, pCO2 ≤ 50 mmHg. SpO2 < 90%. Oxygen therapy improves the condition and normalizes blood gas composition. |
III | Severe dyspnea, breathing with the participation of accessory muscles, respiratory distress up to apnea, tachycardia, ↓SBP. RR:HR ratio is close to 1:2. Skin is pale, generalized cyanosis, skin marbling, and mucosal pallor may be present. The child is lethargic, sluggish. pO2 ≤ 50 mmHg, pCO2 = 75-100 mmHg, SpO2 << 90%. Oxygen therapy is ineffective. |
IV | Hypoxic coma. Earthy skin color, facial cyanosis, cyanotic-purple spots on the trunk and limbs. Consciousness is absent. Convulsive breathing with prolonged apneic pauses. RR is close to 8-10 breaths per minute. Pulse is thready, HR is accelerated or slowed down. SBP is significantly reduced or undetectable. pO2 < 50 mmHg, pCO2 >100 mmHg. SpO2 is not detectable. |
1.6 Clinical presentation of the disease or condition
The clinical presentation of bronchiolitis does not depend on the type of virus. The disease usually develops on the 2nd-5th day of an acute upper respiratory infection and most often proceeds with a low-grade fever, characterized by a cough progressing over 3-4 days, and expiratory or mixed dyspnea [3,13,14,15].
In premature infants, apnea may be the first clinical manifestation of bronchiolitis [3].
It should be noted that the clinical manifestations of bronchiolitis in children are dynamic and characterized by rapid changes.
Bronchiolitis is characterized by: tachypnea of 50-70 breaths per minute, fine moist rales and/or crepitations in the lungs bilaterally, and dry wheezes are also frequently detected.
Visual inspection may reveal chest hyperinflation, and percussion reveals a hyperresonant sound. The progression of respiratory distress may not be accompanied by an increased respiratory rate, manifesting instead as prolonged expiration, participation of accessory muscles in breathing, intercostal retractions, and nasal flaring.
Obstructive syndrome in bronchiolitis reaches its maximum within 1-2 days, then gradually decreases, as does the abundance of rales in the lungs; they usually disappear by days 7-14 [13]. After 3-4 days from the onset of the disease, clinical deterioration with the development of oxygen dependency may be observed. Coughing may sometimes persist for up to 3 weeks [15].
Catarrhal symptoms may be detected.
In bronchiolitis, a child may develop dehydration with metabolic acidosis caused by increased fluid demand due to fever and tachypnea, and reduced fluid intake because the child refuses to drink due to respiratory failure and/or vomiting. In children with severe bronchiolitis complicated by respiratory distress syndrome, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) with hyponatremia and hypervolemia is frequently observed.
2. Diagnostics, medical indications and contraindications for diagnostic methods
The diagnosis of acute bronchiolitis in children is clinical; laboratory, instrumental, and other tests are usually not required for diagnosis [46].
As a rule, tests are performed for etiological or differential diagnosis.
Bronchiolitis manifests as lower airway obstruction occurring against the background of an acute respiratory viral infection (or exposure to irritants) and accompanied by cough and signs of respiratory failure: labored grunting respiration, tachypnea, intercostal and/or subcostal retractions, nasal flaring, and bilateral rales in the lungs. The term "acute bronchiolitis" is used for the first episode of acutely developed bronchobstructive syndrome caused by a viral infection in children in the first two years of life [66].
2.1 Complaints and Anamnesis
See Section 1.6. Clinical Presentation.
When taking a medical history, it is recommended to identify possible risk factors for a severe course of bronchiolitis and assess home care capabilities for the child [2,3,13,14,15].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
2.2 Physical Examination
During the examination, it is recommended to first assess the symptoms of respiratory failure:
Participation of accessory muscles in the breathing act;
Counting the respiratory rate [2,3,13,14,15].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
2.3 Laboratory Diagnostics
To determine treatment tactics, it is recommended to establish the diagnosis of bronchiolitis in a child based on clinical data [2,3,13,14].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comment: Laboratory tests are generally not required to make a diagnosis. A complete blood count (or complete differential blood count) has low diagnostic value. In acute viral bronchiolitis, lymphocytic leukocytosis is frequently observed.
Elevated levels of C-reactive protein (CRP) and procalcitonin (PCT) are not typical.
Upon admission of a child to the hospital, laboratory tests are performed, and the scope is determined by the clinical situation.
In acute bronchiolitis, it is recommended to selectively use rapid respiratory virus detection methods to prevent unjustified antibiotic therapy for this disease [3,14].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comments: Rapid diagnostics for RSV (Rapid immunochromatographic test of nasopharyngeal swab, aspirate, or wash for respiratory syncytial virus) in nasopharyngeal mucosa swabs, as well as PCR testing (Molecular biological study of nasopharyngeal mucosa swabs for respiratory syncytial virus (Human Respiratory Syncytial virus, Detection of respiratory syncytial virus RNA (Human Respiratory Syncytial virus)) in children receiving prophylactic palivizumab** is pharmacoeconomically justified, since due to the extremely low probability of a recurrent RSV infection in the current year, administration of the drug should be discontinued [2].
A positive result of a rapid test or polymerase chain reaction (PCR) test for RSV in most cases confirms its etiological role in the development of bronchiolitis [2]. However, routine identification of viruses in bronchiolitis is rarely necessary due to the wide range of microorganisms potentially causing this disease. In addition, the detection of certain viruses does not always indicate their etiological role; for example, rhinovirus can be detected for a long time after a previous respiratory infection. On the other hand, literature data indicate a decrease in the unjustified use of antibacterial drugs when rapid tests for respiratory viruses are used [16,17]. Also, determining the etiology of viral bronchiolitis may be important for predicting the subsequent development of bronchial asthma in a child.
2.4 Instrumental Diagnostics
Chest X-ray examination (Chest radiography) for bronchiolitis is not recommended routinely unless the child has symptoms suggestive of pneumonia (see relevant clinical guidelines) [2,3,13]. Pneumonia must be ruled out if T0 >380 for more than 3 days, symptoms of toxicity are present, percussion sound is shortened, or rales are asymmetrical.
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comments: Chest X-rays in patients with bronchiolitis often reveal lung hyperinflation, enhanced bronchovascular markings, areas of decreased transparency of lung tissue, and small atelectases, which are sometimes mistakenly interpreted as pneumonia, leading only to unjustified prescribing of antibiotics.
Atelectases in acute (viral) bronchiolitis resolve spontaneously within several days to several weeks (on average up to 15 days) [45].
To determine the severity of respiratory failure in bronchiolitis and, accordingly, the patient management tactics, it is recommended to monitor blood oxygen saturation (including after inhalation of drugs from the groups "Adrenergics for inhalation use" (ATX code – R03A), "Adrenergics in combination with anticholinergics" (ATX code – R03AL), or "Anticholinergics" (bronchodilators) (ATX code – R03BB)) [2,3].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comment: pulse oximetry should be used; blood gas analysis (determination of blood oxygen level, blood carbon dioxide level) and acid-base balance (ABB) (determination of acid-base balance and blood gases) are required only in cases of severe respiratory impairment.
During treatment, follow-up pulse oximetry and/or monitoring of vital signs (blood pressure, heart rate, respiration rate, blood oxygen saturation, diuresis) are performed, and when necessary (typically in severe cases) – blood gas analysis (determination of blood oxygen level, blood carbon dioxide level) and acid-base balance (ABB) (determination of acid-base balance and blood gases) [47].
It is recommended to selectively perform echocardiography and lung ultrasound in patients with acute bronchiolitis for a more accurate assessment of their condition and prediction of the need for respiratory support [48].
GCR CLOE 4Grade of Recommendation C (Level of Evidence 4).
Comment: performed in an inpatient setting.
Echocardiography – for patients with risk factors (e.g., presence of congenital heart defects or other cardiac pathology).
Lung ultrasound – if feasible and available specialists trained in the technique.
2.5 Other Procedures
Diagnostics and treatment of acute bronchiolitis are recommended to be carried out with the participation of a pediatrician / general practitioner (family physician) / neonatologist, and if necessary, an anesthesiologist-resuscitologist, pulmonologist, and other specialists [43].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
2.6 Differential Diagnosis
Bronchiolitis is recommended to be differentiated from other conditions presenting with bronchial obstruction syndrome, such as bronchial asthma [2,3,13,14,15].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comments: Asthma symptoms are typically accompanied by wheezing and prolonged expiration, which appear as early as days 1–2 of the illness.
In addition, the differential diagnosis should include the following nosological entities:
obstructive bronchitis;
pneumonia;
chronic bronchial and/or pulmonary diseases, such as infantile neuroendocrine cell hyperplasia [67];
foreign body aspiration;
aspiration pneumonia;
congenital heart and great vessel defects with heart failure.
However, it should be noted that in a number of situations, severe bronchiolitis develops in children against the background of persistent subclinical airway obstruction, for example, in the presence of vascular rings. Anamnestic data on the absence of a prior upper respiratory tract infection, episodes of choking during eating or drinking, growth retardation, signs of atopy, etc., may assist in differential diagnosis. Appropriate instrumental and laboratory methods are also used [18].
Persistence of symptoms of bronchial obstruction and dyspnea for 6 weeks or more, or their relapse after a "lucid interval" (lasting from 1-2 weeks to 1-2 months), progressive increase in respiratory failure (against the background of persistent fevers in adenovirus infection) indicates the development of post-infectious obliterative bronchiolitis, a rare nosological form primarily caused usually by adenovirus infection (serotypes 3, 7, and 21) and bacterial superinfection. Post-infectious obliterative bronchiolitis is characterized by a chronic course with the development of fibrosis in the small airways, leading in some cases to the formation of a "Swyer-James (hyperlucent) lung". Computed tomography may reveal: a mosaic lung pattern due to "air trapping", the "tree-in-bud" sign, and in some cases, bronchiectasis, usually of a cylindrical nature [19,20,68].
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 Conservative Treatment
The main objective of bronchiolitis therapy is the relief of respiratory failure.
It is recommended to ensure upper airway patency to improve the general condition of the child using short courses of decongestants and other topical nasal preparations (sympathomimetics); the use of nasal aspirators is possible [15].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comment: Cleaning the upper respiratory tract may somewhat alleviate the child's condition. At the same time, there is no strong evidence of its effect on the course of bronchiolitis. There is evidence that deep insertion of a nasopharyngeal mucus aspiration catheter should not be performed routinely [2].
Antibiotics in acute bronchiolitis are not recommended except in situations where there is a concomitant bacterial infection or a serious suspicion of it [2,3,13,15,21].
RR ALE 1Recommendation Readiness Level A (Level of Evidence 1).
Comments: The efficacy and safety of managing children with acute bronchiolitis without antibiotic therapy has been proven both in Russia and abroad. Treatment is carried out in accordance with relevant clinical guidelines
It is not recommended to routinely use systemic antiviral drugs in children with acute bronchiolitis due to the lack of data on their efficacy [2,13,15,22].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comment: currently, there is insufficient evidence regarding the effect of antiviral drugs on the course of bronchiolitis [2].
It is recommended to ensure that a child with bronchiolitis has adequate hydration. The main route is oral. If oral hydration is not feasible, fluid should be administered via a nasogastric tube or intravenously [2].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comments: if drinking is impossible, as well as in grade II-III exicosis (dehydration), parenteral rehydration is necessary. For this purpose, sodium chloride** (0.9% solution) (ATC code: B05CB01) or complex sodium chloride solution [Potassium chloride+Calcium chloride+Sodium chloride]** (ATC code: B05BB01) should be used. However, given the likelihood of syndrome of inappropriate antidiuretic hormone secretion and the risk of pulmonary edema, the volume of intravenous infusions should be limited and not exceed 20 ml/kg/day [23]. The administration volume should be calculated according to the degree of exicosis.
Oxygen therapy (standard humidified oxygen therapy) is recommended when SpO2 ≤92-94% [13, 15, 24].
Level of Recommendation CLevel of Evidence 5Level of recommendation C (Level of evidence 5).
Comment: there is currently no consensus on the exact SpO2 value at which oxygen therapy should be initiated in children with acute bronchiolitis, but most specialists recognize the need to supply oxygen until this parameter stably reaches 95% [2,3,24].
In the absence of an effect from oxygen therapy (standard humidified oxygen therapy), high-flow nasal cannula oxygen therapy is used [46].
If there is no effect, the child is indicated for treatment in the pediatric intensive care unit [46]. (See sections 3.3 and 6)
It is not recommended to routinely use inhalations of "Adrenergic agents for inhalation" (ATC code – R03A) or "Adrenergic agents in combination with anticholinergic agents" (ATC code – R03AL) or "Anticholinergic agents" (ATC code – R03BB) (bronchodilators) in children with bronchiolitis, since in most cases inhalation bronchospasmolytic therapy does not affect the duration of bronchiolitis [2,25].
RR ALE 1Recommendation Readiness Level A (Level of Evidence 1).
Comments: Some children with acute bronchiolitis may develop bronchospasm as part of the disease. Therefore, many foreign guidelines allow the use of drugs for the treatment of obstructive airway diseases as trial therapy in doses specified in the drug instructions. Achieving an effect from the inhalation of drugs for the treatment of obstructive airway diseases within 20 minutes (an increase in SpO2, a decrease in respiratory rate by 10-15 breaths per minute, a decrease in the intensity of wheezing, a decrease in intercostal retractions) and easier breathing justifies continuing inhalation therapy [15]. In the absence of an effect, further inhalations with drugs for the treatment of obstructive airway diseases are pointless [44].
- for example, #salbutamol** (ATC code: R03AL02) at a dose of 0.15 mg/kg per inhalation (maximum 1.25 mg for children under 1 year and 2.5 mg for children over 1 year), diluted in 2–3 ml of 0.9% #sodium chloride** solution or as a metered-dose inhaler for 2 to 4 puffs via a valved holding chamber with a face mask [69,70] or #ipratropium bromide+fenoterol** as an inhalation solution of 25 mg/kg of body weight (calculated for fenoterol) and 12.5 mg/kg of body weight (calculated for ipratropium bromide) + 2 ml of 0.9% #sodium chloride** solution per inhalation [70] or #ipratropium bromide** 125 mcg (0.5 ml) for children under 6 months or 250 mcg (1 ml) for children over 6 months [71].
Routine use of hypertonic (3%) #sodium chloride** solution via nebulizer is not recommended due to the likelihood of bronchospasm [26].
The efficacy of this intervention is not universally accepted [26]. A positive effect of inhaled hypertonic #sodium chloride** therapy in acute viral bronchiolitis has been noted by several researchers [27,28] and is recommended by the AAP (American Academy of Pediatrics) for children hospitalized with bronchiolitis [2]. In a number of children, inhalation of hypertonic #sodium chloride** solution may cause bronchospasm; it is not used in children under 3 months of age.
It is not recommended to routinely use glucocorticoids (inhaled, ATC group – R03BA) (ICS) for bronchiolitis due to the lack of evidence of their clinical effect [2,29].
(Recommendation grade A (Level of evidence 1).
Comment: these drugs may be used if necessary during intensive care (off-label for Acute bronchiolitis), for example, if the child has bronchopulmonary dysplasia [72].
It is not recommended to use systemic corticosteroids for bronchiolitis due to their inefficacy [2,29].
RR ALE 1Recommendation Readiness Level A (Level of Evidence 1).
Comment: these drugs may be used if necessary during intensive care (off-label for Acute bronchiolitis)
3.2 Surgical Treatment
Not required
3.3 Other Treatment
It is not recommended to routinely use vibration and/or percussion massage, as in most cases it also does not have a pronounced effect in patients with bronchiolitis [2,30].
RG BLOE 2Recommendation grade B (Level of evidence 2).
Comments: traditional techniques and forced expiration techniques do not lead to differences in bronchiolitis severity or any other outcomes, do not improve health status, and may lead to severe adverse effects. Currently, data on novel physical therapy methods are insufficient, and further studies are needed to determine their effects and potential use in children with mild bronchiolitis; the efficacy of combining chest physical therapy with hypertonic #sodium chloride** solution also requires study.
High-frequency chest wall oscillation may be used selectively in patients with mild-to-moderate acute bronchiolitis to reduce the severity of respiratory symptoms [46,49].
In children with acute bronchiolitis, when indicated, it is recommended to perform respiratory therapy under the control of blood gas analysis and acid-base balance to relieve respiratory failure and eliminate hypoxemia [46].
GRL CLEL 5Grade of Recommendation C (Level of Evidence 5).
Comments: The choice of respiratory therapy method is made individually depending on indications and capabilities (NCPAP [nCPAP], NIPPV, high-frequency oscillatory ventilation, mechanical ventilation [MV] can be used) [47]. If the child requires invasive mechanical ventilation, the mode and parameters of mechanical ventilation are determined individually depending on the clinical situation.
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Not required
5. Prevention and Dispensary Observation
5.1 Prevention
To reduce the incidence of acute respiratory infections and bronchiolitis in particular among infants, it is recommended to breastfeed for at least the first 6 months of life [31,32] (Recommendation grade B (Level of evidence 3), prevent passive smoking [33,34,35,36,63] (Recommendation grade A (Level of evidence 1), observe hygiene standards, and minimize contacts, especially with individuals showing signs of respiratory infection [37,38,39,40,46,63].
RG ALOE 1Recommendation grade A (Level of evidence 1).
It is recommended to observe anti-epidemic measures in hospitals caring for children of an age vulnerable to acute viral bronchiolitis in order to prevent outbreaks of acute bronchiolitis [46,50,51,52].
RG CLOE 5Recommendation grade C (Level of evidence 5).
Comment: thermometry and examination should be performed for early detection of cases, timely etiological diagnosis, cohorting and isolation of patients, monitoring compliance with current disinfection and air purification regimens, wearing medical masks, wiping stethoscopes with ethanol**, etc.
It is recommended for passive immunization to prescribe a drug from the "Specific immunoglobulins" group – palivizumab** (ATC code J06BB) for the prevention of RSV infection:
Children under 6 months of age born at 35 weeks of gestation or earlier;
Children under 2 years of age who required treatment for bronchopulmonary dysplasia within the last 6 months (respectively, all children in their 1st year of life);
Children under 2 years of age with hemodynamically significant congenital heart defects.
[2,3,41,42, 53,54,55,56,57,58,59,73,74,75,76].
GCR BLOCE 1Grade of Recommendation B (Level of Evidence 1)
Comment: #palivizumab** (ATC code J06BB) is administered intramuscularly at a dose of 15 mg/kg; the course consists of 5 injections at one-month intervals regardless of the season [59,60]. The immunization schedule is determined by current regional/local regulatory documents. Contraindications to immunization: hypersensitivity to palivizumab** (ATC code J06BB), any of the excipients of the drug, or other specific immunoglobulins.
Children with congenital heart disease (CHD) after cardiac surgery using cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) who have received RSV immunoprophylaxis require an additional dose of Palivizumab** immediately after stabilization of their condition.
It is recommended to administer #palivizumab** for passive immunization based on individual indications for the prevention of severe RSV infection at a single dose of 15 mg/kg of the child's body weight. The drug is administered intramuscularly, preferably into the anterolateral thigh. Injections are given monthly regardless of the season – 5 injections, with an allowable deviation of ±5 days [60,77]:
in newborns and premature infants with severe neuromuscular pathology (myotonia, muscular dystrophy) affecting respiratory function, peripheral nervous system diseases, neuromuscular junction disorders, periventricular leukomalacia, and cerebral palsy in cases where impaired respiratory function is documented;
in patients with congenital airway anomalies, interstitial lung diseases, and congenital diaphragmatic hernia;
in children with genetically determined pathologies affecting the bronchopulmonary system, e.g., cystic fibrosis, primary ciliary dyskinesia – for one season;
in children with Down syndrome – for one season;
in patients with primary or secondary immunodeficiencies, primary or secondary bone marrow hypoplasia or aplasia, various humoral or cellular immune defects, including children up to 24 months after internal organ transplantation or hematopoietic stem cell transplantation [59,61,62].
LeR CLoE 5Level of Recommendation C (Level of Evidence — 5)
Comments: the decision on passive immunization with #palivizumab** in patients with the above diseases and conditions is made by a medical board (consilium) based on the risk assessment of severe RSV infection.
It is recommended to vaccinate against influenza in accordance with the National Immunization Schedule for children from 6 months of age in the absence of contraindications to prevent diseases caused by influenza virus, including acute bronchiolitis [78].
Level of Evidence CGrade of Recommendation 5Level of Clinical Effectiveness C (level of evidence – 5)
Comments: vaccinating pregnant women against influenza in accordance with relevant clinical guidelines protects the child up to 6 months of age (the age from which immunization of children is permitted) against this infection [https://cr.minzdrav.gov.ru/recomend/288_2]. Persons in the child's immediate circle should also be vaccinated against influenza, so-called "cocooning" vaccination (to prevent influenza in people in close contact with the child and, consequently, infection of the infant) [79].
5.2 Dispensary monitoring
Dispanserny observation is carried out for children with severe bronchiolitis and/or persistent respiratory symptoms.
Children are monitored in accordance with the recommendations for the underlying premorbid condition that caused the development of severe bronchiolitis.
To monitor the child's condition, they are examined by a pediatrician, neonatologist, general practitioner (family physician), or pulmonologist. The appointment should include a standard physical examination and pulse oximetry. Additional tests are prescribed if complications or the development of chronic lung disease are suspected, including post-infectious obliterans bronchiolitis.
6. Organization of Medical Care
6.1 Indications for hospital admission
Children with acute bronchiolitis are hospitalized in a pediatric infectious disease or boxed pediatric ward.
Indications for the hospitalization of children with bronchiolitis include:
Apnea.
Signs of grade 2–3 respiratory failure.
Age under 6 months in preterm infants.
Undernutrition.
Dehydration, feeding difficulties, lethargy.
Need for continuous upper airway suctioning in a clinical setting.
Burdened premorbid background.
Social indications.
6.1.1. Indications for transfer to the intensive care unit:
Inability to maintain saturation above 92% on oxygen therapy.
Pronounced respiratory muscle fatigue.
Recurrent apnea.
6.1.2. Indications for mechanical ventilation with continuous positive airway pressure (CPAP):
Severe respiratory distress;
Apnea;
Shallow breathing;
Decreased pain response;
Hypoxemia, persistence of cyanosis while breathing 40% O2;
Drop in PaO2 <60 mm Hg;
Increase in PaCO2 >55 mm Hg (hypoventilation);
Need for oxygen therapy with an inspired oxygen fraction FiO2 >0.5.
It is hypothesized that adding helium during CPAP improves carbon dioxide washout and enhances oxygenation due to the transformation of turbulent airflow into laminar flow.
Length of hospital stay is typically no more than 1 week, rarely longer; the patient may be discharged with residual manifestations (rhinitis, wheezing) to avoid superinfection.
6.2 Indications for patient discharge from a medical organization
Criteria for hospital discharge:
Stable saturation >94% on room air.
Absence of respiratory distress.
Adequate nutrition (ability to take food and fluids orally at least 75% of the usual daily requirement).
7. Additional Information
7.1 Outcomes and prognosis
The prognosis after acute bronchiolitis is generally favorable.
Respiratory symptoms may persist for approximately 3 weeks.
About half of the children who have had acute bronchiolitis may subsequently experience episodes of bronchial obstruction. Among them, patients with a family history of atopy are more common, for whom bronchiolitis may be one of the risk factors for developing bronchial asthma [3]. It is hypothesized that patients with a response to bronchodilator therapy may be classified into the risk group for bronchial asthma [80].
Rarely, post-infectious obliterans bronchiolitis may develop, characterized by a chronic course with the development of fibrosis and obliteration of the bronchiolar lumen, leading to disability.
Criteria for Evaluating the Quality of Medical Care
Criteria for assessing the quality of specialized medical care for children with acute bronchiolitis (ICD-10 codes: J21: J21.0; J21.8; J21.9, B97.4)
No. | Quality assessment criteria | Evaluation of compliance |
|---|---|---|
1. | Pulse oximetry and/or 24-hour bedside monitoring of vital functions and parameters (blood pressure measurement, pulse assessment, respiratory rate measurement, blood oxygen level assessment, urine volume determination) were performed. | Yes/No |
2. | Chest X-ray was performed (if body temperature rose above 38 °C for more than 3 days, in the presence of toxic symptoms, with dullness on percussion, or with asymmetric wheezing). | Yes/No |
3. | Oxygen therapy was performed until saturation reached 92% or higher (in case of saturation less than 92% and in the absence of medical contraindications). | Yes/No |
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Appendix A1. Working Group Composition
Baranov A.A. Honorary President of the Russian Union of Pediatricians, Advisor to the Head of the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Chief freelance pediatric specialist of the Ministry of Health of Russia;
Namazova-Baranova L.S. Academician of the RAS, Professor, D.Sc. (Medicine), President of the Russian Union of Pediatricians, Past President of EPA/UNEPSA, Head of the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Head of the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Chief freelance pediatric specialist for preventive medicine of the Ministry of Health of Russia;
Alekseeva A.A. Ph.D. (Medicine), Deputy Head of the Consultative and Diagnostic Center for Children, Pediatrician, Head of the Multidisciplinary Pediatric Day Hospital, Allergist-Immunologist, Leading Researcher at the Department of Clinical Immunology and Allergology, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Member of the Russian Union of Pediatricians
Artemova I.V. Pediatrician, University Clinic, Member of the Russian Union of Pediatricians;
Bakradze M.D. D.Sc. (Medicine), Head of the Department of Diagnostics and Rehabilitative Treatment, National Medical Research Center for Children's Health of the Ministry of Health of Russia, Head of the Department of Children's Diseases, Faculty of Advanced Medical Training, M.F. Vladimirsky Moscow Regional Research Clinical Institute (MONIKI), Member of the Russian Union of Pediatricians (participation in the original version of the document);
Belyaeva I.A. D.Sc. (Medicine), Head of the Department of Preconceptional, Antenatal, and Neonatal Medicine, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Russian Union of Pediatricians, Honorary Professor of the Russian Association of Perinatal Medicine Specialists
Vishneva E.A. D.Sc. (Medicine), Professor of the RAS, Press Secretary of the Russian Union of Pediatricians, Deputy Head for Science, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University);
Davydova I.V. Chief Researcher, National Medical Research Center for Children's Health of the Ministry of Health of Russia, D.Sc. (Medicine), Member of the Russian Union of Pediatricians;
Ivardava M.I. Ph.D. (Medicine), Head of the General Pediatrics Department, Pediatrician, Head of the Department for the Development of Scientific Approaches to the Management of Children with Motor Disorders, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Member of the Russian Union of Pediatricians
Kulichenko T.V. D.Sc. (Medicine), Professor of the RAS, World Health Organization Expert, Head of the Directorate for the Implementation of Functions of the National Medical Research Center for Pediatrics, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Russian Union of Pediatricians;
Polyakova A.S. Ph.D. (Medicine), Member of the Russian Union of Pediatricians;
Privalova T.E. Ph.D. (Medicine), Associate Professor, Head of Academic Affairs at the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Ministry of Health of Russia, Leading Researcher at the Department of Social Pediatrics and Organization of Multidisciplinary Support for Children, Head of Department/Pediatrician, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Member of the Russian Union of Pediatricians
Selimzyanova L.R. Ph.D. (Medicine), Leading Researcher, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Associate Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Ministry of Health of Russia, Associate Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Member of the Russian Union of Pediatricians;
Tatochenko V.K. Professor, D.Sc. (Medicine), Advisor to the Director, National Medical Research Center for Children's Health of the Ministry of Health of Russia, WHO Expert, Member of the Russian Union of Pediatricians;
Turti T.V. D.Sc. (Medicine), Chief Researcher at the Department of Preconceptional, Antenatal, and Neonatal Medicine, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Russian Union of Pediatricians
Novik G.A. Doctor of Medical Sciences, Professor, Head of the Professor I.M. Vorontsov Department of Children's Diseases, Faculty of Postgraduate and Continuing Professional Education, Saint Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation, Vice-President of the Russian Union of Pediatricians, Chief Pediatric Allergist-Immunologist of the Ministry of Health of Russia in the Northwestern Federal District of the Russian Federation
Ovsyannikov D.Yu. D.Sc. (Medicine), Professor, Head of the Department of Pediatrics, People's Friendship University of Russia named after Patrice Lumumba
Platonova M.M. Ph.D. (Medicine), Leading Researcher, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Pulmonologist;
Fedoseenko M.V. Ph.D. (Medicine), Head of the Department for the Development of Scientific Approaches to the Immunization of Patients with Health Status Deviations and Chronic Diseases, Leading Researcher, Pediatrician, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Associate Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Russian Union of Pediatricians
Efendieva K.E. Ph.D. (Medicine), Deputy Head for International Relations and Educational Activities, Leading Researcher, Allergist-Immunologist, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Centre of Surgery, Associate Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Russian Union of Pediatricians.
The authors declare no financial support or conflicts of interest that need to be disclosed.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
Pediatricians;
Neonatologists;
General practitioners (family physicians);
Medical students;
Residents in training.
Methods used for evidence collection/selection: electronic database search.
Description of methods used to assess the quality and strength of evidence: the evidence base for the recommendations includes publications indexed in the Cochrane Library, EMBASE, MEDLINE, and PubMed databases. The search depth is 7 years.
Methods used to assess the quality and strength of evidence:
expert consensus;
assessment of significance in accordance with the rating scheme.
Methods used for evidence analysis:
reviews of published meta-analyses;
systematic reviews with evidence tables.
Description of methods used for evidence analysis
When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The result of this examination affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendations.
To minimize potential bias, each study was evaluated independently. Any discrepancies in evaluations were discussed by the full panel of authors. If a consensus could not be reached, an independent expert was involved.
Evidence tables: compiled by the authors of the clinical guidelines.
Methods used to formulate the recommendations: expert consensus.
Good Practice Points (GPPs)
Recommended good clinical practice is based on the clinical experience of the authors of these guidelines.
Economic analysis
Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.
Recommendation validation method
External expert review.
Internal expert review.
Description of the recommendation validation method
The draft of these recommendations was reviewed by independent experts who were primarily asked to comment on how comprehensible the interpretation of the evidence underlying the recommendations is.
Feedback was obtained from primary care physicians regarding the readability of these guidelines and their assessment of the importance of the proposed recommendations as a tool for daily practice.
All comments received from the experts were thoroughly systematized and discussed by the members of the working group (authors of the recommendations). Each item was discussed individually.
Consultation and peer review
The draft recommendations were reviewed by independent experts who were primarily asked to comment on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.
Working Group
For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.
Key recommendations
1. Levels of evidence (LoE) rating scale for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1. | Systematic reviews of studies controlled by a reference method or systematic review of randomized controlled trials with meta-analysis |
2. | Individual studies controlled by a reference method or individual randomized controlled trials and systematic reviews of studies of any design, except for randomized controlled trials, with meta-analysis |
3. | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4. | Non-comparative studies, case report |
5. | Only mechanism of action justification or expert opinion is available |
2. Levels of evidence (LoE) rating scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)
LoE | Definition |
|---|---|
1. | Systematic review of randomized controlled trials with meta-analysis |
2. | Individual randomized controlled trials and systematic reviews of studies of any design, except for randomized controlled trials, with meta-analysis |
3. | Non-randomized comparative studies, including cohort studies |
4. | Non-comparative studies, case report or case series description, case-control study |
5. | Only justification of the mechanism of action of the intervention (pre-clinical studies) or expert opinion is available |
Table 3. Scale for grading grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
Order of the Ministry of Health and Social Development of the Russian Federation No. 366n of April 16, 2012, "On Approval of the Procedure for Providing Pediatric Care";
Order of the Ministry of Health and Social Development of the Russian Federation No. 521n of May 5, 2012, "On Approval of the Procedure for Providing Medical Care to Children with Infectious Diseases."
Order of the Ministry of Health of the Russian Federation No. 203n dated May 10, 2017 "On approval of criteria for assessing the quality of medical care"
Federal Law No. 489-FZ dated December 25, 2018, "On Amendments to Article 40 of the Federal Law 'On Compulsory Medical Insurance in the Russian Federation' and the Federal Law 'On the Fundamentals of Public Health Protection in the Russian Federation' regarding Clinical Guidelines".
Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, "On Approval of the Procedure and Timeframes for the Development and Revision of Clinical Guidelines, Their Template Form, and Requirements for Their Structure, Composition, and Scientific Validity of Information Included in Clinical Guidelines".
Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017 "On approval of the nomenclature of medical services".
Order of the Ministry of Health of the Russian Federation (Ministry of Health of Russia) dated December 20, 2012, No. 1183n, Moscow, "On Approval of the Nomenclature of Positions of Medical and Pharmaceutical Workers."
State Register of Medicines https://grls.rosminzdrav.ru
** – a medicinal product included in the Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on June 9, 2023) "On Approval of the List of Vital and Essential Medicines, as well as Lists of Medicinal Products for Medical Use and the Minimum Assortment of Medicinal Products Necessary for the Provision of Medical Care"
# – The use of a medicinal product in accordance with indications (characteristics) not specified in the instructions for its use (off-label) is carried out by the decision of the medical commission subject to a signed informed voluntary consent (in accordance with Federal Law No. 323-FZ dated November 21, 2011, as amended).
Clinical classification of bronchiolitis
The clinical classification of bronchiolitis is based on etiology and also includes systemic diseases in which bronchiolitis develops as one of the syndromes [9]:
Bronchiolitis caused by inhalation of various substances:
Smoke inhalation-induced bronchiolitis
Bronchiolitis caused by exposure to irritant gases and mineral dust
Organic dust inhalation-induced bronchiolitis
Infectious bronchiolitis (viral)
Post-infectious (obliterating) bronchiolitis
Drug-induced bronchiolitis
Collagenosis-associated bronchiolitis
Inflammatory bowel disease-associated bronchiolitis
Post-transplant bronchiolitis
Paraneoplastic pemphigus-associated bronchiolitis
Neuroendocrine cell hyperplasia with bronchiolar fibrosis
Diffuse panbronchiolitis
Cryptogenic bronchiolitis
Other:
Familial forms of follicular bronchiolitis
Bronchiolitis in immunodeficiencies
Bronchiolitis in lysinuria
Bronchiolitis in ataxia-telangiectasia (Louis-Bar syndrome)
Bronchiolitis in IgA nephropathy
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Acute bronchiolitis is inflammation occurring in the bronchioles (structural components of the lungs located after the bronchi, which are small tubes) and small bronchi.
The cause of acute bronchiolitis is viruses, most commonly the respiratory syncytial virus (RSV). Virtually all children contract RSV infection in the first 2 years of life (90%), yet only about 20% of them develop bronchiolitis, which may be due to the presence of predisposing factors.
The disease develops in children under 2 years of age (most commonly in children under 1 year of age).
Bronchiolitis typically develops on days 2–5 of an acute upper respiratory infection, usually presents with a low-grade fever, is characterized by a cough worsening over 3–4 days, dyspnea ("heavy" breathing) with expiratory difficulty, and may present with visible intercostal retractions, suprasternal notch retractions (the area located anteriorly between the neck and chest), and nasal flaring.
Bronchiolitis can be most severe in children born extremely prematurely, those with severe congenital heart, vascular, and lung defects, bronchopulmonary dysplasia, and certain types of immunodeficiencies.
Additionally, exposure to tobacco smoke can worsen the course of bronchiolitis.
A child with bronchiolitis may develop dehydration due to increased fluid requirements caused by fever and tachypnea, reduced fluid intake resulting from the child refusing to drink, and/or vomiting.
If signs of bronchiolitis appear, you should consult a doctor immediately.
Treatment for bronchiolitis is prescribed by a physician depending on the severity of the disease manifestations.
Prevention of bronchiolitis:
To reduce the incidence of acute respiratory infections and bronchiolitis in particular, one should try to maintain breastfeeding for at least the first 6 months of life, avoid smoking indoors where the child is present, and follow hygiene rules if there are individuals with an acute respiratory infection in the vicinity (see patient information in the Russian clinical guidelines for Acute Respiratory Viral Infection (ARVI) in children).
Infants in the first year of life belonging to risk groups generally undergo passive immunization against respiratory syncytial virus infection. Check with your pediatrician (neonatologist) to see if this medication is indicated for your child.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Not used