Asthma Management Handbook

Considering alternative diagnoses in children

Recommendations

Consider features that increase or reduce the probability of asthma.

Table. Findings that increase or decrease the probability of asthma in children

Asthma more likely

Asthma less likely

More than one of:

  • wheeze
  • difficulty breathing
  • feeling of tightness in the chest
  • cough

Any of:

  • symptoms only occur when child has a cold, but not between colds
  • isolated cough in the absence of wheeze or difficulty breathing
  • history of moist cough
  • dizziness, light-headedness or peripheral tingling
  • repeatedly normal physical examination of chest when symptomatic
  • normal spirometry when symptomatic (children old enough to perform spirometry)
  • no response to a trial of asthma treatment
  • clinical features that suggest an alternative diagnosis

AND

Any of:

  • symptoms recur frequently
  • symptoms worse at night and in the early morning
  • symptoms triggered by exercise, exposure to pets, cold air, damp air, emotions, laughing
  • symptoms occur when child doesn’t have a cold
  • history of allergies (e.g. allergic rhinitis, atopic dermatitis)
  • family history of allergies
  • family history of asthma
  • widespread wheeze heard on auscultation
  • symptoms respond to treatment trial of reliever, with or without a preventer
  • lung function measured by spirometry increases in response to rapid-acting bronchodilator
  • lung function measured by spirometry increases in response to a treatment trial with inhaled corticosteroid (where indicated)

Sources

British Thoracic Society (BTS), Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the management of Asthma. A national clinical guideline. BTS/SIGN, Edinburgh, 2012. Available from: https://www.brit-thoracic.org.uk/guidelines-and-quality-standards/asthma-guideline

Respiratory Expert Group, Therapeutic Guidelines Limited. Therapeutic Guidelines: Respiratory, Version 4. Therapeutic Guidelines Limited, Melbourne, 2009.

Asset ID: 12

Close
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • British Thoracic Society, Scottish Intercollegiate Guidelines Network, 2012 1
  • Respiratory Expert Group Therapeutic Guidelines Limited, 2009 2

Do not assume that cough is due to asthma in the absence of wheezing or breathlessness. Misdiagnosis of asthma in a child with nonspecific cough can result in overtreatment in children.

How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • Gibson et al. 2010 3

If cough is a prominent symptom, investigate according to the current Australian Cough Guidelines.

How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • Gibson et al. 2010 3

Consider the following alternative diagnoses before making a clinical diagnosis of asthma:

  • bronchiolitis (babies)
  • tracheobronchitis (croup)
  • sleep-disordered breathing
  • inhaled foreign body
  • structural airway problems (e.g. tracheomalacia, bronchopulmonary dysplasia, malformation causing narrowing of intrathoracic airways, vascular ring anomaly compressing bronchus)
  • infections (e.g. recurrent respiratory tract infections, chronic rhinosinusitis, protracted bacterial bronchitis)
  • chronic suppurative lung disease (e.g. consider cystic fibrosis, immune deficiency, primary ciliary dyskinesia or chronic aspiration as underlying cause)
  • aspiration (e.g. due to gastro-oesophageal reflux, discoordinated swallowing, anatomical connection such as tracheo-oesophageal fistula or laryngeal cleft, or neurodevelopmental abnormalities)
  • congenital heart disease
  • other upper airway disease (e.g. rhinosinusitis, postnasal drip, obstructive sleep apnoea, upper airway dysfunction)
  • tumours
  • pulmonary oedema.

Table. Conditions that can be confused with asthma in children

Conditions characterised by cough

Pertussis (whooping cough)

Cystic fibrosis

Airway abnormalities (e.g. tracheomalacia, bronchomalacia)

Protracted bacterial bronchitis in young children

Habit-cough syndrome

Conditions characterised by wheezing

Upper airway dysfunction

Inhaled foreign body causing partial airway obstruction

Tracheomalacia

Conditions characterised by difficulty breathing

Hyperventilation

Anxiety

Breathlessness on exertion due to poor cardiopulmonary fitness

Source

Weinberger M, Abu-Hasan M. Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Pediatrics 2007; 120: 855-64. Available from: http://pediatrics.aappublications.org/content/120/4/855.full

Asset ID: 11

Close
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

More information

Definition of wheeze

Wheeze is defined as a continuous, high-pitched sound coming from the chest during expiration.45 It is a non-specific sign caused by turbulent air flow due to narrowing of intrathoracic airways and indicates expiratory airflow limitation, irrespective of the underlying mechanism4 (e.g. bronchoconstriction or secretions in the airway lumen).

Inspiratory sounds (e.g. rattling or stridor) should not be described as ‘wheeze’.6

Various forms of noisy breathing, including wheezing, are common among babies and preschoolers.4 Noisy breathing is particularly common among infants under 6 months old, but only a small proportion have wheeze.4

Parents and doctors sometimes use the word ‘wheeze’ to mean different things,4, 6 including cough, gasp, a change in breathing rate or style of breathing. If based on parental report alone, children may be labelled as having wheeze when they do not have narrowed airways and expiratory flow limitation.4

There are no validated questionnaire-based instruments to identify wheeze in preschoolers,4 so wheezing is best confirmed by listening with a stethoscope during an episode.

Reported noisy breathing that responds to bronchodilator therapy is likely to be genuine wheeze and to be caused, at least in part, by constriction of airway smooth muscle.4

Close
Significance of wheeze in children 0–5 years

Approximately one in three children has at least one episode of wheezing before their third birthday,4 and almost half of all children have at least one episode of wheezing by age 6 years.4

Wheezing is the most common symptom associated with asthma in children aged 5 years and under.5 Among people with a diagnosis of asthma at any time in their life, approximately 80% will have shown signs of respiratory disease, such as wheezing, in the first years of life.7

However, the presence of wheeze does not mean a child has asthma or will develop asthma:

  • wheezing in infants up to 12 months old is most commonly due to acute viral bronchiolitis or to small and/or floppy airways
  • wheezing in children aged 1–5 years is usually associated with viral upper respiratory tract infections, which recur frequently in this age group.4, 5 Many children wheeze when they have viral respiratory infections, even if they do not have asthma5
  • among preschoolers with recurrent wheezing, only approximately one in three will have asthma at age 6 years7
  • wheezing can also be due to many conditions other than asthma, including anatomical abnormalities of the airways, cystic fibrosis, bronchomalacia.4
Close
Classification of symptom patterns in children

The pattern and severity of symptoms in a child with asthma or wheezing disorder is a guide to initial treatment.

Table. Definitions of asthma patterns in children aged 0–5 years not taking regular preventer

Category

Pattern and intensity of symptoms (when not taking regular treatment)

Infrequent intermittent asthma

Symptom-free for at least 6 weeks at a time (flare-ups up to once every 6 weeks on average but no symptoms between flare-ups)

Frequent intermittent asthma

Flare-ups more than once every 6 weeks on average but no symptoms between flare-ups

Persistent asthma

Mild

At least one of:

  • Daytime symptoms more than once per week but not every day
  • Night-time symptoms more than twice per month but not every week

Moderate

Any of:

  • Daytime symptoms daily
  • Night-time symptoms more than once per week
  • Symptoms sometimes restrict activity or sleep

Severe

Any of:

  • Daytime symptoms continual
  • Night-time symptoms frequent
  • Flare-ups frequent
  • Symptoms frequently restrict activity or sleep

† Symptoms between flare-ups. A flare-up is defined as a period of worsening asthma symptoms, from mild (e.g. symptoms that are just outside the normal range of variation for the child, documented when well) to severe (e.g. events that require urgent action by parents and health professionals to prevent a serious outcome such as hospitalisation or death from asthma).

Note: Use this table when the diagnosis of asthma can be made with reasonable confidence (e.g. a child with wheezing accompanied by persistent cough or breathing difficulty, no signs or symptoms that suggest a potentially serious alternative diagnosis, and the presence of other factors that increase the probability of asthma such as family history of allergies or asthma).

Asset ID: 14

Close

Table. Definitions of asthma patterns in children aged 6 years and over not taking regular preventer

Category

Pattern and intensity of symptoms (when not taking regular treatment)

Infrequent intermittent asthma †

Symptom-free for at least 6 weeks at a time (flare-ups up to once every 6 weeks on average but no symptoms between flare-ups)

Frequent intermittent asthma

Flare-ups more than once every 6 weeks on average but no symptoms between flare-ups

Persistent asthma

Mild

FEV1 ≥80% predicted and at least one of:

  • Daytime symptoms more than once per week but not every day
  • Night-time symptoms more than twice per month but not every week

Moderate

Any of:

  • FEV1 <80% predicted
  • Daytime symptoms daily
  • Night-time symptoms more than once per week
  • Symptoms sometimes restrict activity or sleep

Severe

Any of:

  • FEV1 ≤60% predicted
  • Daytime symptoms‡ continual
  • Night-time symptoms frequent
  • Flare-ups frequent
  • Symptoms frequently restrict activity or sleep

† It may not be appropriate to make the diagnosis of asthma in children aged 6 or older who wheeze only during upper respiratory tract infections. These children can be considered to have episodic (viral) wheeze.

‡ Symptoms between flare-ups. A flare-up is defined as a period of worsening asthma symptoms, from mild (e.g. symptoms that are just outside the normal range of variation for the child, documented when well) to severe (e.g. events that require urgent action by parents and health professionals to prevent a serious outcome such as hospitalisation or death from asthma).

Asset ID: 15

Close
For children already taking regular preventer treatment, adjustments to the treatment regimen are based on finding the lowest dose of medicines that will maintain good control of symptoms.
Close
Short-term and long-term wheezing patterns in children: 0–5 years

Patterns of childhood wheezing over the short term

Classifying a child’s current pattern of symptoms can be useful for making immediate management decisions. The following descriptions of wheezing patterns apply to the pattern of symptoms in children aged 0–5 years and are sometimes used in clinical trials:

Episodic (viral) wheeze: episodes of wheezing (e.g. for a few days when child has a viral cold), but no wheezing between episodes.45

Multiple-trigger wheeze: episodes of wheezing from time to time, with cough and wheeze between episodes when child does not have a viral cold (e.g. when the child cries, plays or laughs).45

However, these patterns are not stable over time and have limited use in predicting whether or not a wheezing preschool child will have asthma by primary school age.89 An individual child is likely to show a different pattern within one year.8

Patterns of childhood wheezing over the long term

Longitudinal population-based cohort studies1011 of preschool children with wheezing have identified various long-term patterns (wheezing phenotypes).4

Table. Systems for retrospectively classifying the duration of childhood wheeze

Classification system/source Phenotypes identified Description
Tucson Children’s Respiratory Study † ‡ Transient wheeze

Wheezing commences before the age of 3 years and disappear by age 6 years

Persistent wheeze

Wheezing continues until up to or after age 6 years

Late-onset wheeze

Wheezing starts after age 3 years.

Avon Longitudinal Study of Parents and Children § Transient early wheeze

Wheezing mainly occurs before 18 months, then mainly disappears by age 3.5 years

Not associated with hypersensitivity to airborne allergens

Prolonged early wheeze

Wheezing occurs mainly between age 6 months and 4.5 years, then mainly disappears before child’s 6th birthday

Not associated with hypersensitivity to airborne allergens

Associated with a higher risk of airway hyperresponsiveness and reduced lung function at age 8–9 years, compared with never/infrequent wheeze phenotype

Intermediate-onset wheeze

Wheezing begins sometime after age 18 months and before 3.5 years.

Strongly associated with atopy (especially house mite, cat allergen), higher risk of airway hyperresponsiveness and reduced lung function at age 8–9 years, compared with never/infrequent wheeze phenotype

Late-onset wheeze

Wheezing mainly begins after age 3.5 years

Strongly associated with atopy (especially house mite, cat allergen, grass pollen)

Persistent wheeze

Wheezing mainly begins after 6 months and continues through to primary school

Strongly associated with atopy

Notes

Terms can only be identified after the child has stopped wheezing for several years and cannot be applied to a preschool child.

Transient wheeze, persistent wheeze and late-onset wheeze can be episodic or multiple-trigger wheeze.#

Sources

† Martinez FD, Wright AL, Taussig LM et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995; 332: 133-8. Available from: http://www.nejm.org/doi/full/10.1056/NEJM199501193320301#t=article

‡ Morgan WJ, Stern DA, Sherrill DL et al. Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med 2005; 172: 1253-8. Available from: http://ajrccm.atsjournals.org/content/172/10/1253.long

§ Henderson J, Granell R, Heron J et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax 2008; 63: 974-80. Available from: http://thorax.bmj.com/content/63/11/974.long

# Brand PL, Baraldi E, Bisgaard H et al. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach [European Respiratory Society Task Force]. Eur Respir J 2008; 32: 1096-110. Available from: http://erj.ersjournals.com/content/32/4/1096.full

Asset ID: 10

Close

Early childhood wheezing phenotypes cannot be recognised or applied clinically, because they are recognised retrospectively.4 In an individual child with episodic wheeze, it is not possible to accurately predict epidemiological phenotype from clinical phenotype.4

Currently available tools for predicting whether a wheezing preschool child will have asthma at school age (e.g. the Asthma Predictive Index7) have limited clinical value.9

Close
Cough and asthma in children

Relationship of cough to asthma in children

  • Misdiagnosis of nonspecific cough as asthma can result in overtreatment in children.
  • Cough can indicate the possibility of a serious underlying illness and warrant further assessment and investigations.3

Table. Red flags for cough in children

Wet or productive cough lasting more than 4 weeks

Obvious difficulty breathing, especially at rest or at night

Systemic symptoms: fever, failure to thrive or poor growth velocity

Feeding difficulties (including choking or vomiting)

Recurrent pneumonia

Inspiratory stridor (other than during acute tracheobronchitis)

Abnormalities on respiratory examination

Abnormal findings on chest X-ray

‘Clubbing’ of fingers

Source

Gibson PG, Chang AB, Glasgow NJ et al., CICADA: Cough in Children and Adults: Diagnosis and Assessment. Australian cough guidelines summary statement. Med J Aust, 2010; 192: 265-71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20201760

Asset ID: 13

Close
Chronic cough (cough lasting more than 4 weeks) without other features of asthma is unlikely to be due to asthma.3

Cough is a frequent symptom in children with asthma, but may have a different mechanism from other symptoms of asthma (e.g. wheeze, chest tightness or breathlessness). Children who have recurrent cough, but do not wheeze, are unlikely to have asthma.12 A very small minority of children with recurrent nocturnal cough, but no other asthma symptoms, may be considered to have a diagnosis of atypical asthma.12  This diagnosis should be only made in consultation  with a paediatric respiratory physician.

In children with no abnormalities detected on physical examination, chest X-ray or spirometry, and no wheezing or breathlessness, chronic cough is most likely:3

  • due to protracted bacterial bronchitis (resolves with 2–6 weeks’ treatment with antibiotics)3
  • post-viral (resolves with time)
  • due to exposure to tobacco smoke and other pollutants.3

Frequency of cough reported by parents correlates poorly with frequency measured using diary cards or by audio recording monitors.13

0-5 years

Most cases of coughing in preschool children are not due to asthma:

  • Recurrent cough in preschool children, in the absence of other signs, is most likely due to recurrent viral bronchitis. Cough due to viral infection is unresponsive to bronchodilators and preventers such as montelukast, cromones or inhaled corticosteroids.
  • Children attending day care or preschool can have a succession of viral infections that merge into each other,13 giving the false appearance of chronic cough (cough lasting more than 4 weeks).

In preschool-aged children, cough may be due to asthma when it occurs during episodes of wheezing and breathlessness or when the child does not have a cold.

6 years and over

Chronic cough may be due to asthma if the cough is episodic and associated with other features of asthma such as expiratory wheeze, exercise-related breathlessness, or airflow limitation objectively demonstrated by spirometry (particularly if responsive to a bronchodilator).3

Close
Alternative diagnoses in children

Other conditions characterised by wheezing, breathlessness or cough can be confused with asthma. These include:

  • protracted bacterial bronchitis314
  • habit-cough syndrome3
  • upper airway dysfunction.6

Table. Conditions that can be confused with asthma in children

Conditions characterised by cough

Pertussis (whooping cough)

Cystic fibrosis

Airway abnormalities (e.g. tracheomalacia, bronchomalacia)

Protracted bacterial bronchitis in young children

Habit-cough syndrome

Conditions characterised by wheezing

Upper airway dysfunction

Inhaled foreign body causing partial airway obstruction

Tracheomalacia

Conditions characterised by difficulty breathing

Hyperventilation

Anxiety

Breathlessness on exertion due to poor cardiopulmonary fitness

Source

Weinberger M, Abu-Hasan M. Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Pediatrics 2007; 120: 855-64. Available from: http://pediatrics.aappublications.org/content/120/4/855.full

Asset ID: 11

Close

Table. Findings that increase or decrease the probability of asthma in children

Asthma more likely

Asthma less likely

More than one of:

  • wheeze
  • difficulty breathing
  • feeling of tightness in the chest
  • cough

Any of:

  • symptoms only occur when child has a cold, but not between colds
  • isolated cough in the absence of wheeze or difficulty breathing
  • history of moist cough
  • dizziness, light-headedness or peripheral tingling
  • repeatedly normal physical examination of chest when symptomatic
  • normal spirometry when symptomatic (children old enough to perform spirometry)
  • no response to a trial of asthma treatment
  • clinical features that suggest an alternative diagnosis

AND

Any of:

  • symptoms recur frequently
  • symptoms worse at night and in the early morning
  • symptoms triggered by exercise, exposure to pets, cold air, damp air, emotions, laughing
  • symptoms occur when child doesn’t have a cold
  • history of allergies (e.g. allergic rhinitis, atopic dermatitis)
  • family history of allergies
  • family history of asthma
  • widespread wheeze heard on auscultation
  • symptoms respond to treatment trial of reliever, with or without a preventer
  • lung function measured by spirometry increases in response to rapid-acting bronchodilator
  • lung function measured by spirometry increases in response to a treatment trial with inhaled corticosteroid (where indicated)

Sources

British Thoracic Society (BTS), Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the management of Asthma. A national clinical guideline. BTS/SIGN, Edinburgh, 2012. Available from: https://www.brit-thoracic.org.uk/guidelines-and-quality-standards/asthma-guideline

Respiratory Expert Group, Therapeutic Guidelines Limited. Therapeutic Guidelines: Respiratory, Version 4. Therapeutic Guidelines Limited, Melbourne, 2009.

Asset ID: 12

Close
Close
Diagnostic difficulties when investigating asthma-like symptoms in adolescents

Asthma is commonly misdiagnosed in young people presenting with exercise-related symptoms or cough.15 Conditions associated with dyspnoea include hyperventilation, anxiety, and poor cardiopulmonary fitness.6

Both denial and overplay of symptoms has been observed among adolescents.15 Adolescents with new or re-emerging asthma symptoms may deny their symptoms.15 US data suggest that risk factors for undiagnosed asthma among adolescents include female sex, smoking (current smoking and exposure to others’ smoke), low socioeconomic status, family problems, low physical activity and high body mass.16

Close
Exercise-related symptoms in adolescents

In adolescents, exercise-related wheezing and breathlessness are poor predictors of exercise-induced bronchoconstriction. Only a minority of adolescents referred for assessment of exercise-induced respiratory symptoms show objective evidence of exercise-induced bronchoconstriction.1

For adolescents with exercise-related symptoms, common conditions that should be considered in the differential diagnosis include poor cardiopulmonary fitness, exercise-induced upper airway dysfunction and exercise-induced hyperventilation.1517

In addition to spirometry, other objective tests (e.g. cardiopulmonary fitness testing, bronchial provocation tests) may be helpful to clarify the diagnosis and inform management.

Close

References

  1. British Thoracic Society (BTS), Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the Management of Asthma. A national clinical guideline. BTS, SIGN, Edinburgh, 2012. Available from: https://www.brit-thoracic.org.uk/guidelines-and-quality-standards/asthma-guideline/
  2. Respiratory Expert Group, Therapeutic Guidelines Limited. Therapeutic Guidelines: Respiratory, Version 4. Therapeutic Guidelines Limited, West Melbourne, 2009.
  3. Gibson PG, Chang AB, Glasgow NJ, et al. CICADA: cough in children and adults: diagnosis and assessment. Australian cough guidelines summary statement. Med J Aust. 2010; 192: 265-271. Available from: http://www.lungfoundation.com.au/professional-resources/guidelines/cough-guidelines
  4. Brand PL, Baraldi E, Bisgaard H, et al. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J. 2008; 32: 1096-1110. Available from: http://erj.ersjournals.com/content/32/4/1096.full
  5. Global Initiative for Asthma (GINA). Global strategy for the diagnosis and management of asthma in children 5 years and younger. GINA, 2009. Available from: http://www.ginasthma.org/
  6. Weinberger M, Abu-Hasan M. Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Pediatrics. 2007; 120: 855-864. Available from: http://pediatrics.aappublications.org/content/120/4/855.full
  7. Castro-Rodriguez JA. The Asthma Predictive Index: a very useful tool for predicting asthma in young children. J Allergy Clin Immunol. 2010; 126: 212-216. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20624655
  8. Schultz A, Devadason SG, Savenije OE, et al. The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze. Acta Paediatr. 2010; 99: 56-60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19764920
  9. Savenije OE, Kerkhof M, Koppelman GH, Postma DS. Predicting who will have asthma at school age among preschool children. J Allergy Clin Immunol. 2012; 130: 325-331. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22704537
  10. Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. N Engl J Med. 1995; 332: 133-138. Available from: http://www.nejm.org/doi/full/10.1056/NEJM199501193320301#t=article
  11. Henderson J, Granell R, Heron J, et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax. 2008; 63: 974-980. Available from: http://thorax.bmj.com/content/63/11/974.long
  12. van Asperen PP. Cough and asthma. Paediatr Resp Rev. 2006; 7: 26-30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16473813
  13. Bush A. Diagnosis of asthma in children under five. Prim Care Respir J. 2007; 16: 7-15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17297521
  14. Craven V, Everard ML. Protracted bacterial bronchitis: reinventing an old disease. Arch Dis Child. 2013; 98: 72-76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23175647
  15. Towns SJ, van Asperen PP. Diagnosis and management of asthma in adolescents. Clin Respir J. 2009; 3: 69-76. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20298380
  16. Yeatts K, Davis KJ, Sotir M, et al. Who gets diagnosed with asthma? Frequent wheeze among adolescents with and without a diagnosis of asthma. Pediatrics. 2003; 111: 1046-54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12728087
  17. Tilles SA. Exercise-induced respiratory symptoms: an epidemic among adolescents. Ann Allergy Asthma Immunol. 2010; 104: 361-7; 368-70, 412. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20486325