Respiratory Distress Flashcards

1
Q

What are the questions you ask in the history of a child presenting with respiratory distress?

A

Establish what the parent or carer is worried about.

Note what symptoms there are and how long they have been going on for.

Specifically find out about recent activities suggesting foreign body ingestion (make no assumptions relating to a young baby’s age: an older toddler may try to ‘feed’ the new baby) and anaphylactic reaction.

Foreign body ingestion

Specifically find out about past respiratory disease.

Complete usual paediatric history. When enquiring about social history in a young child, enquire about smokers in the house (relatives, frequent visitors).

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2
Q

What are the suggestive features of foreign body ingestion?

A

Suggestive features: witnessed episode, sudden onset of coughing or choking, recent history of playing/eating small objects.

Effective coughing suggested by: crying or verbal response to questions, being able to take breath in before coughing, loud cough, fully responsive child.

Ineffective coughing suggested by: inability to vocalise, quiet or silent cough, inability to breathe, cyanosis, decreasing level of consciousness

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3
Q

Which questions do you ask about a past history of asthma?

A

Previous severe asthma.
Previous hospitalisations.
Dependence on inhaled or systemic corticosteroids.
Non-compliance with medications.
Labile asthma with pronounced diurnal obstruction.
Brittle asthma with unexpected sudden deterioration of airway function.
Chronic asthma with depressive symptoms/manipulative use of asthma.

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4
Q

What do you assess in an examination for respiratory distress?

A

General observations.

Respiratory system

  • Assess chest expansion and auscultate beware of the silent chest (this means that very little air is going in and out).
  • Pulse oximetry should show an oxygen saturation close to 100% in normal healthy children breathing air.
  • Acute severe asthma is defined by an SpO2 ≤92%, respiration rate raised and the child being unable to talk in normal sentences

Other systems - these need assessing to gauge to what extent the respiratory distress has affected them:
-Cardiac system - tachycardia is generally seen (the heart rate should roughly be four times the normal respiratory rate) - eg, pulse ≥140 beats per minute (bpm) (2-5 years) or ≥150 bpm (≥5 years old) in acute severe asthma.

NB: bradycardia occurs in the presence of severe or prolonged hypoxia and is a pre-terminal sign.

  • Skin colour - pallor occurs initially. Cyanosis is a late and pre-terminal sign.
  • Agitation ± drowsiness. This may be difficult to assess and the parents will need to be consulted in the case of the very young child or baby.
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5
Q

What are the signs of respiratory distress?

A

Tachypnoea: very slow RR in children suggest imminent respiratory arrest or poisoning with narcotic drugs.

Intercostal and sternal recession: Intercostal and abdominal muscles are drawn in with each inspiration. This is seen more easily in very young children; therefore, it is particularly significant if seen in the child over 6-7 years of age.

Use of accessory muscles: look for the head bobbing up and down in infants.

Tripodding or anchoring: The child may sit forward and grasp their feet or hold on to the side of the bed.

Nasal flaring: particularly seen in infants

Inspiratory/expiratory noises:

  • Stridor: high-pitched inspiratory noise - sign of upper airway obstruction.
  • Wheezing: tends to be louder on expiration - sign of smaller-calibre lower airway obstruction.
  • Grunting: exhalation against a partially closed glottis - sign of severe respiratory distress in infants.
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6
Q

What are the causes of respiratory distress?

A

Laryngomalacia.
Foreign body ingestion.
Laryngeal oedema: anaphylaxis, inhalation injury.
Upper respiratory tract infection: epiglottitis, croup, retropharyngeal abscess.
Lower respiratory tract causes: asthma, bronchiolitis and bronchitis, pneumonia, acute respiratory distress syndrome.

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7
Q

What are the clinical clues to alternative diagnoses other than asthma in wheezy children?

A

Symptoms present from birth or perinatal lung problem: cystic fibrosis, chronic lung disease of prematurity, ciliary dyskinesia, developmental lung anomaly.

Family history of unusual chest disease: cystic fibrosis, neuromuscular disorder.

Severe upper respiratory tract disease: defect of host defence, ciliary dyskinesia.

Persistent moist cough: cystic fibrosis, bronchiectasis, protracted bacterial bronchitis, recurrent aspiration, host defence disorder, ciliary dyskinesia.

Excessive vomiting: gastro-oesophageal reflux (with or without aspiration).

Paroxysmal coughing bouts leading to vomiting: pertussis.

Dysphagia: swallowing problems (with or without aspiration).

Breathlessness with light headedness and peripheral tingling: dysfunctional breathing, panic attacks.

Inspiratory stridor: tracheal or laryngeal disorder.

Abnormal voice or cry: laryngeal problem.

Focal signs in chest: developmental anomaly, post-infective syndrome, bronchiectasis, tuberculosis.

Finger clubbing: cystic fibrosis, bronchiectasis.

Failure to thrive: cystic fibrosis, host defence disorder, gastro-oesophageal reflux.

Focal or persistent chest radiological changes: developmental lung anomaly, cystic fibrosis, post-infective disorder, recurrent aspiration, inhaled foreign body, bronchiectasis, tuberculosis.

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8
Q

Management of respiratory distress

A

Life-threatening respiratory distress warrants immediate initiation of life support measures and immediate ambulance transfer to hospital.

Children with moderate-to-severe respiratory distress should be referred to the local paediatric team.

Where the decision is made to treat the child at home, parental education and frequent reviews are mandatory.

Almost all ill (or injured) children will benefit from high-concentration oxygen therapy. The only small group of infants to be careful with are those with duct-dependent congenital heart disease.

It is usually counterproductive to make an unwilling child wear an oxygen mask. Avoid any other action that may agitate the child (which worsens the respiratory distress) unless the child is critically ill.

Most of the assessment and initiation of treatment can be done with the child in their parent’s arms.

Do not put anything (including a thermometer) in the mouth of a child with stridor as this may precipitate complete respiratory obstruction).

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9
Q

What is croup?

A

Croup is a common childhood illness causing symptoms which may involve a harsh barking cough, hoarse voice and (inspiratory) stridor.

It is usually caused by inflammation of the upper respiratory tract (predominantly the larynx and trachea but it may affect the bronchi) as a result of viral infection.

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10
Q

What is the pathophysiology of croup?

A

Viral upper respiratory tract infection (URTI) causes nasopharyngeal inflammation that may spread to the larynx and trachea, causing subglottal inflammation, oedema and compromise of the airway at its narrowest portion.

The movement of the vocal cords is impaired leading to the characteristic cough. Occasionally, fibrinous exudation with pseudomembrane formation may occur, causing further airway compromise.

It is thought that some children who experience recurrent bouts of spasmodic croup have a primarily allergic rather than infective aetiology for subglottal oedema

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11
Q

What are the causative organisms for croup?

A

Parainfluenza virus types I, II, III and IV (thought to be responsible for about 80% of cases - type I causing 50-70% of severe cases).

Respiratory syncytial virus.

Adenoviruses.

Rhinoviruses.

Enteroviruses.

Measles.

Metapneumovirus.

Influenza A and B (type A is associated with severe disease).

Mycoplasma pneumoniae (rare cause).

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12
Q

What are the risk factors for croup?

A

Croup most often affects children aged 6 months to 3 years.

More prevalent in autumn and spring.

Genetic studies suggest that the C/C variant of the CD14 C-159T gene has a significantly lower prevalence of croup.

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13
Q

Presentation of croup

A

Croup normally starts with nonspecific symptoms of viral URTI, such as runny nose, sore throat, fever and cough.

This progresses over the course of a couple of days to include the characteristic barking cough and hoarseness. These symptoms tend to be worse at night.

There is a high degree of variability in clinical findings. There may be a mild-to-moderate fever. Check vital signs (including temperature, pulse and blood pressure).

A barking cough and hoarse cry are nearly always present.

Stridor (harsh, low-pitched noise heard during inspiration) may be heard at rest or only when the child is agitated or active.

Chest sounds are usually normal but can be decreased in volume where there is severe airflow limitation.

Respiratory distress with marked tachypnoea and intercostal recession may be noted.

It should be recognised that a child whose stridor appears to be improving and in whom intercostal recession has disappeared may in fact be deteriorating with worsening airways obstruction. Such a child may be at high risk of complete airway occlusion.

Drowsiness, lethargy, and cyanosis despite increasing respiratory distress should be considered as red flags for impending respiratory failure.

The illness tends to last for about 3-7 days but can persist for up to two weeks.

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14
Q

Differentials for croup

A
Epiglottitis 
Inhaled foreign body 
Inhaled noxious substance 
Acute anaphylaxis 
Bacterial tracheitis 
Diphtheria 
Laryngomalacia 
Peritonsillar abscess (quinsy) 
Retropharyngeal abscess 
Angioneurotic oedema
Vocal cord paralysis
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15
Q

Which scoring system is used to assess the severity of croup?

A

Westley clinical scoring system.

• The modified Westley clinical scoring system for croup

Inspiratory stridor:
o Not present - 0 points.
o When agitated/active - 1 point.
o At rest - 2 points.

Intercostal recession:
o	Not present - 0 points.
o	Mild - 1 point.
o	Moderate - 2 points.
o	Severe - 3 points.

Air entry:
o Normal - 0 points.
o Mildly decreased - 1 point.
o Severely decreased - 2 points.

Cyanosis:
o None - 0 points.
o With agitation/activity - 4 points.
o At rest - 5 points.

Level of consciousness:
o Normal - 0 points.
o Altered - 5 points.

Possible score 0-17: 0-3 = mild croup, 4-6 = moderate croup, >6 =severe croup.

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16
Q

When is immediate hospital assessment for croup indicated?

A

Moderate or severe croup, or impending respiratory failure.

Any suspicion of epiglottitis, bacterial tracheitis, peritonsillar abscess, retropharyngeal abscess, or laryngeal diphtheria.

Any suspicion of inhaled foreign body, angioneurotic oedema, hypocalcaemic tetany, or ingestion of corrosives.

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17
Q

When is admission to hospital required in a child with croup?

A

History of severe obstruction, previous severe croup, or known structural upper airways abnormalities (eg, laryngomalacia, tracheomalacia, vascular ring, Down’s syndrome).

Age less than 6 months.

Immunocompromised.

Inadequate fluid intake.

Poor response to initial treatment.

Uncertain diagnosis.

Significant parental anxiety, late evening or night-time presentation, the child’s home is a long way from the hospital, or the parents have no transport.

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18
Q

What are the investigations for croup?

A

A low SaO2 on pulse oximetry (<95%) indicates significant respiratory impairment.

It is important to weigh the benefits of investigations such as CXRs and blood tests against the risks of distressing the child and making the symptoms worse.

A rapid influenza A test can be performed if it is considered vital to do so but even this investigation (which requires a throat swab) can distress the child.

Direct or indirect laryngoscopy is not usually required but may be employed where the course of the illness is atypical or there is reason to suspect a congenital or other alternative cause for upper airway obstruction.

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19
Q

What is the management of croup?

A

Do not give antibiotics unless there are sound clinical reasons to suspect secondary bacterial infection.

Keep the child as calm and as comfortable as possible. Allow the child to remain in a parent’s arms and avoid any unnecessary painful interventions. Persistent crying increases oxygen demands and respiratory muscle fatigue and worsens the obstruction.

Use paracetamol or ibuprofen to control any discomfort from symptoms or fever.

Ensure an adequate fluid intake.

Do not advise humidified air (eg, steam inhalation).

Mild croup is largely self-limiting but treatment with a single dose of a corticosteroid (eg, dexamethasone 150 micrograms/kg) by mouth may be of benefit.

More severe croup (or mild croup that might cause complications) requires hospital admission. A single dose of a corticosteroid (eg, dexamethasone 150 micrograms/kg or prednisolone 1-2 mg/kg by mouth) should be administered before transfer to hospital.

In hospital, dexamethasone 150 micrograms/kg (by mouth or by injection), prednisolone 1-2 mg/kg by mouth or budesonide 2 mg (by nebuliser) will often reduce symptoms. The dose may need to be repeated after 12 hours if necessary

Nebulised adrenaline (epinephrine) is usually reserved for patients in moderate-to-severe distress.

Nebulised adrenaline (epinephrine) solution 1 in 1,000 (1 mg/mL) should be given with close clinical monitoring in a dose of 400 micrograms/kg (maximum 5 mg) repeated after 30 minutes if necessary

20
Q

What are the complications of croup?

A

Bacterial superinfection may result in pneumonia or bacterial tracheitis. The most frequent organism is Staphylococcus aureus, followed by group A streptococcus, Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenzae and anaerobes.

Pulmonary oedema, pneumothorax, lymphadenitis and otitis media have also been reported.

Inability to maintain adequate fluid intake may lead to dehydration.

21
Q

What is anaphylaxis?

A

Anaphylaxis is a severe, life-threatening, generalised or systemic hypersensitivity reaction which is likely when both of the following criteria are met:
• Sudden onset and rapid progression of symptoms.
• Life-threatening airway and/or breathing and/or circulation problems.

Skin and/or mucosal changes (flushing, urticaria, angio-oedema) can also occur but are absent in a significant proportion of cases.

22
Q

What is the cause of an anaphylactic reaction?

A

An anaphylactic reaction occurs when an allergen reacts with specific IgE antibodies on mast cells and basophils (type 1 hypersensitivity reaction), triggering the rapid release of stored histamine and the rapid synthesis of newly formed mediators.

These cause capillary leakage, mucosal oedema and ultimately shock and asphyxia.

Anaphylactic reactions can vary in severity and rate of progression - they may progress rapidly (over a few minutes) or occasionally in a biphasic manner.

Rarely, manifestations may be delayed by a few hours (adding to diagnostic difficulty) or persist for more than 24 hours.

Anaphylactoid reactions are not IgE-mediated but cause similar mast cell activation.

23
Q

What are the triggers of an anaphylactic reaction?

A
Foods: 
o Peanuts 
o Pulses 
o Tree nuts such as almond and hazelnut 
o Fish and shellfish 
o Eggs 
o Milk 
o Sesame 

Venom:
o Bee stings
o Wasp stings

Drugs: 
o Antibiotics 
o Opioids 
o NSAIDs 
o IV contrast media 
o Muscle relaxants
24
Q

What is the presentation of anaphylaxis?

A

There is often (but not always) a history of previous sensitivity to an allergen, or recent history of exposure to a new drug (eg, vaccination).

Initially, patients usually develop skin symptoms, including generalised itching, urticaria and erythema, rhinitis, conjunctivitis and angio-oedema.

Signs that the airway is becoming involved include itching of the palate or external auditory meatus, dyspnoea, laryngeal oedema (stridor) and wheezing (bronchospasm).

General symptoms include palpitations and tachycardia (as opposed to bradycardia in a simple vasovagal episode at immunisation time), nausea, vomiting and abdominal pain, feeling faint - with a sense of impending doom; and, ultimately, collapse and loss of consciousness.

Airway swelling, stridor, breathing difficulty, wheeze, cyanosis, hypotension, tachycardia and prolonged capillary filling suggest impending severe reaction.

If no history is available in a collapsed patient, use an ABCDE advanced life-support approach.

25
Q

Differentials for anaphylaxis

A
Sepsis 
Life-threatening asthma- most common in children
Vasovagal epidode 
Panic attack 
Breath-holding episode in a child.
26
Q

Emergency treatment of anaphylaxis

A
  • A, B, C, D, E
  • Consider anaphylaxis when there is compatible history of rapid-onset severe allergic-type reaction with respiratory difficulty and/or hypotension, especially if there are skin changes present.
  • Give high-flow oxygen - using a mask with an oxygen reservoir (greater than 10 litres min-1 to prevent reservoir collapse).
  • Lay the patient flat:
  • Raise the legs (with care, as this may worsen any breathing problems).
  • In pregnant patients, use a left lateral tilt of at least 15° (to avoid caval compression).
  • Adrenaline (epinephrine)- IM in the anterolateral aspect of the middle third of the thigh (safe, easy, effective)
  • IV fluid challenge

Chlorphenamine

Hydrocortisone

Continuing respiratory deterioration requires further treatment with a bronchodilator, such as salbutamol (inhaled or IV), ipratropium (inhaled), aminophylline (IV) or magnesium sulfate (IV - unlicensed indication). Magnesium is a vasodilator and can compound hypotension and shock.

Monitor pulse oximetry, ECG and BP

27
Q

Doses of adrenaline used in anaphylaxis

A

Adult IM dose 0.5 mg IM (= 500 mcg = 0.5 ml of 1:1000)

Child IM dose:
>12 years: 0.5 mg IM (500 mcg= 0.5 ml of 1:1000)
6-12 years: 300 mcg IM (0.3 ml)
Less than 6 years: 150 micrograms IM (0.15 ml)

IM adrenaline (epinephrine) should be repeated after 5 minutes if there is no clinical improvement.

Patients requiring repeated IM doses may benefit from IV adrenaline (epinephrine). In these circumstances, expert help is required as soon as possible.

IV adrenaline (epinephrine) should only be administered by those with the necessary training and experience - such as anaesthetists, intensivists and emergency department physicians.

It can be administered as a bolus dose or as an infusion. Patients requiring repeat bolus dosing should commence an infusion of adrenaline (epinephrine).

NB: half doses of adrenaline (epinephrine) may be safer for patients on amitriptyline, imipramine, a monoamine-oxidase inhibitor (MAOI) or a beta-blocker.

28
Q

Doses of IV fluid in anaphylaxis

A

Insert one or more large-bore IV cannulae (enable the highest flow).

Use intraosseous access (if trained to do so) in children when IV access is difficult.

Give a rapid fluid challenge:

  • Adults - 500 mL of warmed crystalloid solution (eg, Hartmann’s or 0.9% saline) in 5-10 minutes if the patient is normotensive or 1 L if the patient is hypotensive.
  • Use smaller volumes (eg, 250 mL) for adult patients with known cardiac failure and use closer monitoring (listen to the chest for crepitations after each bolus).
  • The use of invasive monitoring (eg, central venous pressure (CVP)) can help to assess fluid resuscitation.
  • For children - give 20 mL/kg of warmed crystalloid.
29
Q

Doses of chlorphenamine in anaphylaxis

A

Chlorphenamine (after initial resuscitation). Dose depends on age:
o >12 years and adults: 10 mg IM or IV slowly.
o >6-12 years: 5 mg IM or IV slowly.
o >6 months-6 years: 2.5 mg IM or IV slowly.
o <6 months: 250 micrograms/kg IM or IV slowly.

30
Q

Doses of hydrocortisone in anaphylaxis

A

Hydrocortisone (after initial resuscitation). Dose depends on age:
o >12 years and adults: 200 mg IM or IV slowly.
o >6-12 years: 100 mg IM or IV slowly.
o >6 months-6 years: 50 mg IM or IV slowly.
o <6 months: 25 mg IM or IV slowly.

31
Q

Investigations for anaphylaxis

A

Serum mast-cell tryptase can be measured in cases of anaphylaxis, particularly to clarify diagnosis where ambiguity exists.

Tryptase is the preferred marker for demonstrating mast-cell degranulation (histamine elevation, for example, is very transient).

Levels of serum tryptase, which is a mast-cell specific protease, peak at one hour after an anaphylactic reaction, remaining elevated for approximately six hours.

Elevated serum tryptase levels imply either massive mast-cell degranulation, as occurs in anaphylaxis, or a condition such as mastocytosis.

NICE advises measurement:
o As soon as possible after emergency treatment for anaphylaxis.
o 1-2 hours after onset of first symptoms of anaphylaxis (and no later than 4 hours).

32
Q

What is the follow up management after anaphylaxis?

A

Take a full history from the patient (relatives, friends, and other staff). This should include documenting all symptoms in full, so as to confirm diagnosis. In particular, record the time of onset of the reaction and the circumstances immediately before the onset of symptoms.

Review the patient’s notes and charts. Study both absolute and trends of values relating to vital signs.

Check that important routine medications are prescribed and being given.

Review the results of laboratory or radiological investigations.

Consider what level of care is required by the patient - eg, transport to hospital if in the community.

In the patient’s notes, make complete entries of your findings, assessment and treatment. Record the patient’s response to therapy.

Consider definitive treatment of the patient’s underlying condition.

Refer to an allergist or allergy clinic to try to identify the allergen, so that it can be avoided in future.

Organise self-use of pre-loaded pen injections for future attacks (eg, EpiPen®; containing 0.3 mL of 1 in 1000 strength (that is, 300 micrograms) for adults; and for children 0.3 mL of 1 in 2000 (150 micrograms)). This again may be best done in allergy clinics. It is important that the technique for using these auto-injectors should be demonstrated and taught.

Encourage the patient to wear a medical emergency identification bracelet or similar.

33
Q

What is the criteria for prescribing an epipen?

A

-History of Anaphylaxis
-Previous cardiovascular / Respiratory involvement
-Evidence of airway obstruction
-Poorly controlled Asthma requiring regular inhaled corticosteroids
-Reaction to a small amount of allergen
Ease of allergen avoidance

34
Q

What is bacterial tracheitis?

A

Bacterial tracheitis, also known as bacterial croup, acute laryngotracheobronchitis, or membranous croup, is a potentially lethal infection of the subglottic trachea.

It is often a secondary bacterial infection preceded by a viral infection affecting children most commonly under age six.

Concern for airway protection is the mainstay of treatment as thick, mucopurulent secretions can cause airway narrowing.

35
Q

What is the aetiology of bacterial tracheitis?

A

Bacterial tracheitis is a bacterial infection of the trachea often preceded by a viral upper respiratory infection. The most common viruses implicated include Influenza A and B (with type A being the most common), respiratory syncytial virus (RSV), parainfluenza virus, measles virus, and enterovirus.

These viruses cause airway mucosal damage via a local immune response which predisposes the trachea to the seeding of bacterial infections.

Implicated bacteria include Staphylococcus aureus (most common, including MRSA), Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae type B, and less commonly, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, and anaerobic organisms.

The long-term presence of a tracheostomy is another potential predisposing factor, presumed to be a result of spread from bacterial colonization of the tracheostomy tube.

36
Q

Presentation of bacterial tracheitis

A

Signs and symptoms include stridor (inspiratory or expiratory), fever, productive cough, thick secretions from a tracheostomy when present, and can include frank respiratory distress.

Drooling and tripoding are less common and suggest an alternative diagnosis such as epiglottitis, as children with bacterial tracheitis do not have difficulty swallowing their oral secretions.

Steeple sign is the narrowing of the trachea seen on a CXR.

Candle dripping sign is when there is irregularity or haziness of the tracheal mucosal wall on CXR.

37
Q

Differentials for bacterial tracheitis

A
  • Angioedema
  • Croup
  • Diphtheria
  • Epiglottitis
  • Quinsy
  • TB
38
Q

Management of bacterial tracheitis?

A
  • Prompt assessment of airway compromise.

* Antibacterial management should be broad coverage including MRSA.

39
Q

What is laryngomalacia?

A

Laryngomalacia (LM) is a congenital softening of the larynx that predisposes to dynamic supraglottic collapse during the inspiratory phase of respiration, resulting in intermittent upper airway obstruction and stridor.

The laryngeal structure is malformed and floppy, causing the tissues to fall over the airway opening and partially block it.

LM is the most common source of stridor in infants and the commonest congenital laryngeal anomaly.

40
Q

What is the presentation of laryngomalacia?

A
  • Stridor
  • Onset within 2 weeks of birth
  • Features of airway obstruction such as nasal flaring, intercostal recession and tracheal tug.
  • Resolution of symptoms by 2 years of age.
41
Q

Risk factors for laryngomalacia

A

GORD (reported in 50-100% of patients with LM)

Neurological abnormalities

Laryngeal anatomical abnormalities

Male sex

Genetic syndromic disorder- Down’s syndrome and congenital cardiac disease.

42
Q

Investigations for laryngomalacia

A

Flexible laryngoscopy

43
Q

What is the management of laryngomalacia?

A
GORD management
Surgery (supraglottoplasty) if consider is severe. Indicated: 
o	Life-threatening apnoeas
o	Significant cyanosis 
o	Failure to gain weight with feeding
o	Need of additional oxygen
44
Q

What is type 1 hypersensitivity?

A

In Type 1 hypersensitivity reactions mast-cell activation is induced by secretion of IgE antibodies. Initial exposure to the antigen causes the priming of Th2 cells, and their release of IL-4 causes the B cells to switch their production of IgM to IgE antibodies which are antigen-specific. The IgE antibodies bind to mast cells and basophils, sensitising them to the antigen.

When the antigen enters the body again, it cross links the IgE bound to the sensitised cells, causing the release of preformed mediators including histamine, leukotrienes and prostaglandins.

This leads to widespread vasodilation, bronchoconstriction, and increased permeability of vascular endothelium.

The reaction can be divided into two stages – immediate, in which release of pre-formed mediators causes the immune response, and the late-phase response 8-12 hours later, where cytokines released in the immediate stage activate basophils, eosinophils, and neutrophils even though the antigen is no longer present.

45
Q

What is type 2 hypersensitivity?

A

Type 2 hypersensitivity reactions are mediated by antibodies targeting antigens on cell surfaces.

When cell surface antigens are presented to T cells, an immune response is started, targeting the cells to which the antigens are attached.

Antibodies binding to cells can activate the complement system, leading to degranulation of neutrophils, a release of oxygen radicals, and eventual formation of membrane attack complex – all of which lead to destruction of the cell.

Parts of the complement activation can also opsonise the target cell, marking it for phagocytosis.

The destruction of host cells in this way can lead to tissue-specific damage. Type 2 hypersensitivity reactions may occur in response to host cells (i.e. autoimmune) or to non-self cells, as occurs in blood transfusion reactions.

Type 2 is distinguished from Type 3 by the location of the antigens – in Type 2, the antigens are cell bound, whereas in Type 3 the antigens are soluble.

46
Q

What is type 3 hypersensitivity?

A

•Type 3 hypersensitivity reactions are mediated by antigen-antibody complexes (formed by soluble antigens) in the circulation that may be desposited in and damage tissues. The complexes may become lodged in the basement membranes of tissues which have particularly high rates of blood filtration – the kidney and synovial joints being common targets.

Once lodged, the immune complexes rapidly and significantly activate the complement chain, causing local inflammation and attraction of leucocytes.

Activation of complement results in increased vasopermeability, the attraction and degranulation of neutrophils, and the release of oxygen free radicals which can severely damage surrounding cells.

47
Q

What is type 4 hypersensitivity?

A

Type 4 hypersensitivity reactions are mediated by antigen-specific activated T-cells. When the antigen enters the body, it is processed by antigen-presenting cells and presented together with the MHC II to a Th1 cell.

If the T-helper cell has already been primed to that specific antigen, it will become activated and release chemokines to recruit macrophages and cytokines such as interferon-γ to activate them.

Activated macrophages release pro-inflammatory factors, leading to local swelling, oedema, warmth, and redness. They also secrete lysosomal elements and reactive oxygen species, again leading to local tissue damage. CD8+ T cells may be involved in type 4 reactions where a foreign antigen is detected on a cell, such as in organ rejection: this is known as cell mediated cytotoxicity, and also results in recruitment and activation of macrophages.

This reaction is also known as delayed-type hypersensitivity due to its characteristic longer time period to appear following antigen exposure. The reaction takes longer than all other types because of the length of time required to recruit cells to the site of exposure – around 24 to 72 hours.