Bilirubin needs to be around 60 to see visible jaundice.
AST is less specific than ALT – also produced in kidney, brain etc. But perhaps changes more quickly than ALT. Most important other source of AST and ALT is muscle – so check CK too, especially if bilirubin normal. Myopathies, viral myositis, muscular dystrophy can all present with “abnormal LFTs”.
Gamma GT is also found in other tissues so not 100% specific but typically suggests cholestasis or other biliary problem (together with alkaline phosphatase).
Alkaline phosphatase also produced in bone, so look at calcium, phosphate and vitamin D as well as signs of rickets or renal disease. Most common cause of isolated high alkaline phosphatase is benign transient hyperphosphatasaemia.
Falling transaminases can be ominous in situation of bilirubin, albumin, coagulation deteriorating…
Obesity can mimic asthma, it affects respiratory symptoms and lung mechanics, but it can also overlap of course. Asthma is more often diagnosed in obese (misdiagnosed?). High birth weight is associated. , as is maternal obesity (and gestational weight gain) in pregnancy. Each BMI increase of 1kg/m2 increases risk by 2-3%!
Obesity is one of the factors associated with fatal asthma attacks (but note socioeconomic confounding).
Weight reduction leads to improved lung function, health status, symptoms and morbidity in adults. Not yet proven in adolescents.
Slightly increased risk of acute asthma attacks in obese adults and school age children.
One of the Herpes virus family, and like other herpesviruses (herpes, varicella) becomes latent in the body after infection, in the case of EBV in B-lymphocytes. Immune system has developed specific strategies over the course of human evolution to control it – hence specific immunodeficiencies such as Duncan’s syndrome where EBV appears to be the only infection that becomes problematic (even catastrophic).
Associated with a number of tumours, including non-Hodgkin’s lymphoma, Burkitt Lymphoma (especially in Africa), nasopharyngeal carcinoma.
In most children, a mild febrile illness, with lymphadenopathy (“glandular fever” or infectious mononucleosis), sore throat (can be severe). Failure to improve with antibiotics is a clue! Peak age for severe presentations is teenagers – “kissing disease” (sexually transmitted!? Edinburgh students study found lower rates if routine barrier methods used). Prolonged incubation period of 30-50 days!
Classically rash triggered by amoxicillin (which is why amoxicillin isn’t recommended for sore throats, but rash can be seen with penicillin too) – maculopapular, sometimes petechial and/or urticarial, which is rather more suggestive.
On examination, hepatosplenomegaly can be seen.
Blood film characteristically shows atypical lymphocytosis. Monospot test (for heterophile antibodies) 70-90% sensitive so has false negatives as well as false positives so may need to proceed to PCR if important to know.
Splenic rupture after EBV has been reported but is very rare. Advice usually given to avoid contact sports. In ultrasound studies, peak spleen size is typically noted within the first 2 weeks of illness, but may extend to 3.5 weeks. The majority of spleen injuries occur within the first 21 days of illness and are exceedingly rare at >28 days, so one month avoidance probably sufficient.
=allergic rhinoconjunctivitis due to seasonal triggers, typically grass and/or tree pollen. First described by John Bostock in 1819! More likely if born in early months of year!
So itchy, swollen, watery eyes, runny and/or blocked nose, sneezing. Often itchy throat and ears too. Cobble stone appearance can be seen at the back of throat.
Not dangerous, but can seriously affect quality of life: poor sleep, poor concentration (exams usually at worst time of year), embarrassment about snot. One study showed children in England were less likely to get their predicted exam grades if they had hay fever, especially if prescribed sedating antihistamines. Moderate to severe hay fever also associated with worse, uncontrolled asthma. London study found hospital admissions for asthma 50% higher 3 days after high grass pollen levels (inconclusive for tree pollen). [Int J Biometeorol. 2017]Brussels study found similar, compounded by air pollution. Treatment of hay fever with intranasal steroids or class 2 antihistamines reduced admissions by up to 80%. [asthma res and pract2015]
Associated with other atopic conditions, such as food allergy and asthma. Under recognized as trigger for asthma exacerbations – pollen is too large to trigger the lower airways directly, rather, pollen exposure in the upper airways trigger inflammation that travels down (probably over a period of weeks) to the lower airways. An exception is when pollen grains are fragmented, as seen in thunder storm asthma where one night in Melbourne, 2016, several thousand acute respiratory presentations came to ED (up over 400%), ambulance service was overwhelmed, hospitals ran out of inhalers. 10 deaths implicated. [Australia, Clin Exp Allergy. 2018;48:1421‐1428]. Complex though, rain/moisture probably contribute to pollen grain rupture, and atmospherics bring surges of pollen down to ground level.
There are many different species of grass, but if allergic to one you tend to be allergic to all of them. Trees on the other hand vary, you tend to be allergic to specific groups of trees. In Europe the most important are birch (northern Europe) and olive (Southern Europe). Birch is related to alder, hazel, beech and oak. Olive is related to ash. Weeds belong to various unrelated families.
Hazel trees can start producing pollen in January! Weeds such as nettle can continue producing pollen through September! Moulds seem more associated with asthma than hay fever. Cypress blooms in winter!
It’s not just pollen count – the amount of allergen carried by the pollen (“pollen potency“) varies too. Correlates pretty closely but varies by time and place, 4-5 fold difference geographically (especially grass). France has the highest yearly average grass pollen potency, 7-fold higher than Portugal. Olive pollen from two locations 400km apart varied 4-fold in their allergen potency – in Portugal there are times when pollen from Spain probably more of a problem for triggering hay fever than pollen from “local” trees! [Health Impacts of Airborne Allergen Information Network (HIALINE project)]
Watch the pollen count, and choose activities inside or outside accordingly. There are apps that can help with this. But note that the time of day is important too – for grass pollen, the risk is greatest in the first half of the morning and again from about 4pm in the afternoon, until late evening. But can persist into the early hours if temperatures remain high, this effect is particularly noticeable in the cities of the south of England. For tree pollen, the risk is usually during daylight hours only.
Closing windows, or at least not sitting near windows should help. Wash your hair more regularly. Don’t dry clothes outside. Pollen barrier balms available (evidence?). Big, wrap around sunglasses?
Choose when and where you are going on holiday carefully, so you get away during the worst period. North of Scotland and the islands have a short, late grass season (late June, early July). Coastal areas likely to be best (although often there are fields just back from the coast, so it may depend on the wind direction!). For tree pollen, season is earlier for most (see above), and there are parts of Scotland (Orkney, Lewis, Caithness, Sutherland) with very few trees. For holidays abroad, see World pollen data.
Antihistamines – oral or nasal. Various, some people find one works better than another Sedating antihistamines eg Chlorphenamine should be avoided except at night. Nasal steroids useful if used correctly. Combination steroid/antihistamine available. Leukotriene receptor antagonist licensed for hay fever in children with asthma.
Short courses of oral steroids might be justified for special occasions.
Immunotherapy available – deaths reported in asthmatics with poor control.
Sublingual – age not important cf ability to hold in mouth for 2 minutes. Not approved by SMC in Scotland yet. Combined grass and house dust mite coming.
[Sian Ludman, St Mary’s]
For symptoms all year round (perennial), triggers such as house dust mite and pets are more likely.
Diagnosis is about probability – high probability is recurrent episodes of cough, wheeze, breathlessness, chest tightness plus documented wheeze, atopic history, documented variable PEF or FEV1. Isolated episodic cough is not sufficient. Episodes typically triggered by viral infections, cold air, exertion, laughter or emotion. Start treatment, “typically” 6 weeks inhaled corticosteroids (ICS). If good response to treatment, then diagnosis is confirmed.
If intermediate probability then spirometry with reversibility is preferred initial test for children old enough to do it (Grade D recommendation). If spirometry normal, then do challenge tests and/or Fractional exhaled nitric oxide (FeNO) measurement. For younger children, watchful waiting or trial of treatment.
FeNO has reasonable positive predictive value, but false positives in allergic rhinitis, rhinovirus and dietary nitrates, plus overlap in values between asthmatics and normal population (especially children).
Red flags –
Focal chest signs
Abnormal voice or cry
Failure to thrive
Self management education, written personalized plan. Assess control – consider using Asthma Control Test (ACT) questionnaire or similar.
Assess risk of future attacks. Co-morbid atopic conditions, younger age, obesity, and exposure to environmental tobacco smoke are markers of increased risk (some of these strongly socioeconomically linked, of course).
Ask specifically about medication use and assess prescriptions. Explore attitudes to medication as well as practical barriers to adherence.
Not for routine house dust mite avoidance measures. Avoid smoking and second hand smoke.
Weight loss (including dietary and exercise programmes) for overweight and obese. Breathing exercise programmes can be offered as an adjuvant to pharmacological treatment for adults.
ICS are recommended preventer. An asthma attack in the previous 2 years, symptoms 3 days a week, or using reliever 3 days a week, or waking 1 night a week are indications. Give twice daily at least until good control established.
Start at dose appropriate for the severity of the disease. In mild to moderate asthma, no benefit in starting at high dose and weaning. In children, “reasonable” starting dose is Very Low (100mcg twice daily of Clenil or equivalent).
5yrs and over, if add-on is required then choice between inhaled long acting beta agonist (LABA) or leukotriene receptor antagonist (LTRA). Only then increase dose of ICS from very low (100mcg Clenil or equivalent twice daily) to low (200mcg twice daily).
For exercise induced symptoms, generally just a sign that inadequate control! But if otherwise well controlled then give inhaled short acting beta agonist immediately prior to exercise. Then choice between LRTA, LABA, cromoglicate or theophylline.
Acute Severe Asthma
Sats under 92%
PEF 33-50% of best or predicted
Can’t complete sentences in one breath, or too breathless to feed
HR >140 (under 5), >125 (over 5)
RR>40 (under 5), >30 (over 5)
Life threatening defined as:
Exhaustion, poor resp effort [tautology?]
MDI plus spacer if mild/moderate
If refractory to beta agonist, add ipratropium 250mcg mixed into beta agonist [same dose for everyone]
“Consider adding 150mg magnesium sulphate to each neb in first hour if symptoms started <6hrs and presenting with sats <92%” [Recommendation based on MAGNETIC trial – no overall benefit but better Asthma Severity Score at 1 hour for this subgroup – see below] – 2.5ml of 250mmol/ml (1000mg made up to 16ml)
Give oral steroids early, dose by age.
Second line treatment –
Consider single IV bolus of salbutamol (15mcg/kg over 10mins)
Consider aminophylline for severe asthma unresponsive to maximal doses of bronchodilators and steroids.
Consider IV MgSO4 40mg/kg/d
Systematic review of IV Magnesium in children (2018) – pulmonary function improved, hospitalization and further treatment decreased. MAGNETIC trial of Magnesium nebs did not show a clinically significant improvement in mean asthma severity scores in children with acute severe asthma. Best clinical response was seen in children with saturations <92% at presentation and those with preceding symptoms lasting less than 6 hours [Lancet 2013].
Physiological is because Long chain FAs in breast milk compete with Glucuronyl transferase! Dehydration and poor feeding contribute (jaundice FOLLOWS, does not cause). But can also be seen in bottle fed babies.
Prolonged jaundice defined as 21/7 if well, term according to American Academy of Pediatrics. After that, investigation probably appropriate.
Unconjugated vs Conjugated bilirubin is important – do direct bilirubin. Conj bili >20 may indicate significant disease, esp if unconj not high. Low albumin suggests prenatal onset.
Haemolysis (so liver function tests normal): eg rhesus disease (diagnosis: Direct Coombs Test Positive), ABO, irregular antibodies (Kell, Duffy; varying significance), hereditary sphero/elliptocytosis, G6PD deficiency, DIC. G6PD in baby can be precipitated by maternal drugs/infection. Enzyme assay false negative because of high retic count, so test mother for carrier status.
Crigler Najjar is unconjugated. Uridine Di Phos Glucuronyl transferase deficiency (Dubin Johson/Rotor only present >2 yr). Recessive form is severe, assoc with kernicterus; dominant can be treated with phenobarb.
Galactosaemia – in the first week of life can be unconjugated but always features liver dysfunction cf Crigler Najjar so unlikely to be any confusion.
Suggests hepatitis. Note that Alk phos in normal neonates is often high in isolation. See BSPGHAN protocol.
For suspected asthma, where child unable to do spirometry, then watchful waiting or trial of treatment for specified time period. Choice of treatment depends on severity and frequency of symptoms – “typically 6 weeks inhaled steroid”, “very low dose”.
Start regular preventer treatment or escalate treatment if you are getting frequent symptoms, viz:
three times a week or more, or
using your blue inhaler three times a week or more, or
if your asthma is waking you up once a week or more.
Start regular preventer if asthma attack in previous 2 years!
Same table for all ages now, and same steroid doses!
Step 1 – very low dose inhaled corticosteroid (ICS). OR leukotriene receptor antagonist (LRTA) if under 5.
Step 2 – Add LRTA if under 5, else inhaled long acting Beta agonist (LABA) if 5+.
Step 3 – If no response to LABA, stop and increase ICS dose. If some benefit from LABA continue and increase ICS dose, or consider trial of LTRA.
Step 4 – high dose therapies: increase ICS dose to medium, or add slow release theophylline. Refer for specialist care.
Very low dose is 50mcg 2 puffs twice daily of beclometasone. Low dose is double that, medium 200mcg 2 puffs twice daily.
QVAR and fluticasone are double the efficacy of beclometasone so doses are halved. Ciclesonide is somewhere in between.
An added sound heard when listening with a stethoscope, distinct from heart sounds or other clicks or snaps.
Can indicate a structural abnormality. But can be heard in normal hearts too, esp kids.
Or “innocent” murmur. Characteristic vibratory, crescendo-decrescendo sound, loudest along left sternal border. Never louder than grade 3. Typically gets quieter when child stands up (you would not expect a murmur caused by a structural abnormality to change).
Another innocent one, a rumble heard in the upper chest, disappears when lying down, or when neck turned or neck veins occluded gently.
Pulmonary flow murmur
Pulmonary valve closest to anterior chest wall, which might explain why you sometimes hear this. Might be confused with pulmonary stenosis or subaortic membrane.