Trial by Inhaler - Bronchiolitis vs Viral Wheeze

With wheeze in children becoming a major presentation again, it feels like a good time to explore the issue of deciding whether a child has bronchiolitis or viral induced wheeze.  There are various way that people do this in practice.  Many stick to a strict 12 month cut off.  This method works reasonably well and is rarely problematic.  Bronchospasm is rare below this age and if it is going to be problematic under the age of 12 months, in my experience the infant is severely distressed and gets bronchodilators out of desperation rather than a diagnostic trial.

I have already explored a method of determining whether the pathology causing wheeze is predominantly wetness (bronchiolitis) or tightness (viral induced wheeze/ bronchospasm) by using age combined with the story.

Slow accumulation of moisture and mucous tends to cause worsening of symptoms over days whereas bronchospasm causes acute change over hours.  My opinion is that in the majority of cases, the age and the story will correlate.

Where the patient is in the overlap zone (e.g. 10-15 months old) and the story is clear (e.g. snotty/ coughing on Monday, struggling with feeds on Tuesday, noisy breathing on Wednesday and fast breathing on Thursday) then the story gives the diagnosis.  With age/ story correlation or where the age allows ambiguity but the story is clear, the diagnosis is made.

So what about simply trying an inhaler to see if it works?  This alternative approach to the age of overlap sounds straightforward and is reasonably common in practice, but is it logical?

A therapeutic trial works best when a clinical effect is guaranteed and unambiguous.  Neither of these things is true in this situation.  With viral wheeze, which should respond to salbutamol, clinically apparent response may require increased or repeated doses.  Bronchiolitis, which will not respond, is famous for mini-fluctuations in work of breathing.  This is caused by mucous plugging or the clearing of secretions.

When you think of it in these terms, trying an inhaler doesn't meet the quality standards required of a valid test.

Trial by inhaler is also problematic due to human bias.  Uncertainty is fertile ground for biases to mislead us when an inhaler is given to make a diagnosis rather than as treatment.  It is better to use beta-agonists therapeutically where appropriate and to see non-response as a reason to reconsider a presumed diagnosis of viral wheeze.  If viral wheeze is the problem, we should not allow the lack of effect to refute the diagnosis.

Edward Snelson

@sailordoctor

Disclaimer - when I wrote this, I briefly thought that you could bring logic to medicine.  I know, right?!?

Ipratropium for infant wheeze - a Christmas stocking stuffer

On the run-up to Christmas, this site will be delivering some rather minimalist FOAMed.  Instead of comprehensive explanations, there will be some short but hopefully useful posts for you to enjoy.  Think of them like a stocking stuffer rather than your main present.  Perhaps you'll like this format even better.  [I will never forget the year that my children played more with one of their stocking stuffers than with their main present.  That stocking filler present was a whoopee cushion.]

Here it is:

That little caveat at the end is about the use of ipratropium as an additional agent in the treatment of severe/ life-threatening brochospasm due to viral wheeze.  In that scenario, it's still very much all about the salbutamol.

That's all folks.  If you wanted something bigger, you'll have to wait until we're opening the main Christmas presents, or you could read this post that goes into more detail about infant wheeze diagnosis.

I hope you're looking forward to your next stocking stuffer.

Edward Snelson

@sailordoctor

The Decision Maker's Guide to Bronchiolitis Assessment

 This bronchiolitis season is going to be different.  While SARS-CoV2 virus does not seem to be a significant cause of wheeze in children (1), all the other usual viruses are still out there and will be causing wheeze soon in a child near you.  What might have changed is how we make decisions about that child.

For the purposes of exploring our decision making, it is important to define bronchiolitis as a condition that is a virally induced inflammation of the small airways of the lungs in a child, typically under the age of 1.  It is clinically distinctive from viral induced wheeze which is virally induced bronchospasm of the large airways, typically in a child over the age of 1.  For a separate article on differentiating these two conditions, click this link.

The necessary decisions regarding bronchiolitis haven't changed.  What might change during a global pandemic is the outcome of those decisions.  Hospitals have always been dangerous places, with a significant risk of hospital acquired infection.  That risk has escalated due to the prevalence of the highly infective SARS-CoV2 virus.  Though very unlikely to cause COVID-19 infection in children, there is that risk, the risk of PIMS-TS and the risk of COVID-19 to the accompanying adults.

The aim in bronchiolitis decision making has always been to keep as many children out of hospital as is safe to do so.  In order to do that expertly, we just need to make three decisions.

1. Does this child have bronchiolitis?
2. Should this child be managed at home or in hospital?
3. What treatment should the child be given?

Question 1: Does this child have bronchiolitis?

Most children under the age of 1 year presenting with a tight cough, wheeze, respiratory signs and poor feeding have bronchiolitis.  There are other possible explanations for that presentation however and it is important to know about these other possibilities.

Viral induced wheeze, which involves bronchospasm is separate from bronchiolitis.  Clues that it may be viral induced wheeze include the age of the child (most commonly over 1 year) and previous episodes of viral induced wheeze.  The other clue is the onset of the respiratory changes.  Bronchiolitis is a slow accumulation of wetness in the airways and the history is typically of a gradual and progressive worsening of symptoms over days.  Viral induced wheeze, due to the bronchospasm involved, presents with a more sudden onset of wheeze and distress, often going from normal to significantly abnormal over a few hours.

Pneumonia is almost never associated with wheeze in children (2).  Focal crepitations are often heard in a viral lung infection of any kind.  The presence of wheeze strongly suggests that the signs and symptoms are virally induced in some way.  Infants with pneumonia will tend to be significantly unwell.  The simple rule of thumb is this:  If the infant has a wheeze and is well enough to be managed in a pre-hospital setting, they do not have bacterial pneumonia.

Congestive cardiac failure (CCF) due to haemodynamically significant yet undetected congenital cardiac abnormalities is a rare mimic of bronchiolitis but one that is important to be aware of.  The typical cause is a large ventricular septal defect (VSD) causing a significant left to right shunt.  This increased pressure through the lung circulation causes pulmonary odema which manifests as poor feeding, fine crepitations and wheeze.  Thankfully, most significant heart defects are detected before a baby is discharged from postnatal care, but occasionally one slips through and the signs and symptoms are easily mistaken for bronchiolitis.

There are usually clues however.  A murmur is the most obvious clue but this can be difficult to hear at >160bpm.  An excessive tachycardia is a possible sign of CCF.  A significant hepatomegaly (normal babies often have up to a centimetre of palpable liver) is highly suspicious of CCF.  Finally, the progression of symptoms does not fit for bronchiolitis as they continue to get worse after the 3-4 days in which bronchiolitis reaches its peak.

Putting these things together, it is usually possible to be confident in diagnosing bronchiolitis as long as the history and findings are consistent with bronchiolitis and not one of the other pretenders.

If the diagnosis is bronchiolitis, we can move onto our next question:

Question 2: Should this child be managed at home or in hospital?

Most children with bronchiolitis can be managed in the community.  Keeping people away from hospital where it safe to do so has never been more important.  In the UK, the NICE guidelines for bronchiolitis (3) give recommendations for when to refer and when to consider referral.

Referral is always recommended for red flags.  In the NICE guidelines, these are a combination of signs of potential respiratory failure.  Notably, apnoeas are included as a stand-alone red flag.  That means that a child without any chest signs of severe respiratory distress should still be referred if they have had episodes where they appear to stop breathing.  The reason for this is that in such cases, immature respiratory drive may be a factor.  Following an apnoea, a baby can temporarily seem much improved but may go on to have further events and deteriorate suddenly.

Feeding and hydration is probably the least well defined element of the decision making element.  The guidelines ask the clinician to consider a variety of factors, however being able to assess whether the amount of feeding is adequate is next to impossible apart from overt signs of dehydration.  We never know how much a breast fed baby is getting unless the answer is "nothing."  If the baby is bottle fed, applying a percentage to that as being adequate doesn't take into account the fact that many bottle fed babies take much larger volumes as a baseline.  As a result, the most objective measure of adequate feeding has to be signs of hydration or dehydration.  For that reason, I have included clinical dehydration in the list of red flags and beyond that, feeding difficulties remain a matter of clinical judgement when it comes to referral.

Possibly the most controversial element of the decision making is the presence of risk factors.  In the guidance, it is stated "When deciding whether to refer a child with bronchiolitis to secondary care, take account of any known risk factors for more severe bronchiolitis such as... (e.g.) premature birth, particularly under 32 weeks."  The guideline evidence statement lists the basis for each risk factor listed and with the exception of neuromuscular disease, the committee acknowledged that there is no credible published evidence for the other risk factors.  Apart from neuromuscular disease, they are all consensus opinion recommendations.

So what are you supposed to do when you see an 8 month old baby with mild bronchiolitis, no red flags and adequate feeding when you know that they were born at 31 weeks gestation?  Do you send them to secondary care in case because they have a risk factor for severe bronchiolitis or do you keep them well away from hospital because they don't have severe bronchiolitis and you don't want to add a hospital acquired infection to their list of problems?

Balancing risk vs benefit is what it is all about here.  There is a known risk of hospital acquired infection vs an unknown risk of severe bronchiolitis.  There is also no evidence that admitting high risk children with bronchiolitis is any safer than good safety-netting advice.

If the decision is made to manage a child with bronchiolitis at home, the third and final question is:

Question 3: What treatment should the child be given?

There has been a load of research done to try to find an effective treatment for bronchiolitis.  Supportive interventions (oxygen, CPAP etc) in the cases where respiratory support are needed have been shown to be effective.  Each and every other therapy have in turn shown to have no benefit for mild to moderate uncomplicated bronchiolitis.  Therapies proven to be ineffective include β-agonists, ipratopium, hypertonic saline, antibiotics and corticosteroids.  The bottom line is that for a child being managed in the community, no pharmacological treatment should be given.  This recommendation is consistent  across guidelines from the UK, USA and Australia (3,4,5).

That makes this flowchart nice and simple:

Finally, you might be asking yourself if you are an expert decision maker when it comes to a small person who has a cough and wheeze.  Hopefully this post helps you to feel that you are.  Decision making in such children is all about recognition, knowing the red flags and above all, learning that if in doubt, looking at the child will almost always give you your answer.

Edward Snelson
@sailordoctor

References

1. Roland D, Teo KW, Bandi S, et al COVID-19 is not a driver of clinically significant viral wheeze and asthma Archives of Disease in Childhood Published Online First: 16 October 2020. doi: 10.1136/archdischild-2020-320776
2. Hirsch A, Monuteaux M, Neuman M, Bachur R, Estimating Risk of Pneumonia in a Prospective Emergency Department Cohort, Paediatrics, Vol 204, p172-176.E1, Jan 01, 2019 doi:10.1016/j.jpeds.2018.08.077
3. Bronchiolitis in children: diagnosis and management, NICE guideline [NG9] Published date: 01 June 2015
4. American Academy of Pediatrics Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis, Pediatrics November 2014, 134 (5) e1474-e1502; doi: 10.1542/peds.2014-2742
5. The Royal Children's Hospital Melbourne Clinical Practice Guidelines: Bronchiolitis

Chest X-rays in children - The Wimbledon Rules

We've come a long way in terms of reducing unnecessary tests in paediatrics.  It is within my career that it was standard to obtain a chest X-ray (CXR) for any child presenting with their first episode of wheeze.  Now, such an approach is seen as outdated.  This is a good thing.  In fact the vast majority of acute and sub-acute respiratory presentations in children can be managed without needing a CXR.

In some ways it was a lot easier to know when to do a CXR 20 years ago.  The answer was pretty often.  Every lower respiratory tract infection (LRTI), every first episode of wheeze and every persistent cough tended to result in a CXR.  Now, we should rarely do CXR in those circumstances.  Rarely doesn't mean never though, so how do you know if you're doing too many?  Enter the Wimbledon Rules for CXR in children…  I’ll come to that later.  First, I’ll explore a little bit about the complexities of doing CXRs in paediatrics.

The problem with CXR in children is that it can be misleading.  The most common scenario in which this is true is for the wheezy child.  Wheeze is a strong negative predictor of pneumonia(1).  This makes sense clinically when you think about it.  If an infant or child has restricted lower airways, that is reason enough to have respiratory distress.  If you then take a section of lung out of action, you won't be wondering if they might have a problem.  It is likely to be very obvious from how unwell they are and how abnormal their breathing is.  As a rule, children with tight airways and pneumonia together are in a very bad way.

While wheeze is a strong negative predictor of pneumonia, a CXR in wheezy children is rarely clear.  In many cases there is a patchy white area on the CXR.  This is often at the right heart border, or as it is sometimes called, "the area of radiological romance."  If you do a CXR too often in wheezy children, this will happen fairly frequently and it may be difficult to ignore.

Even if a child does have a LRTI, CXR is not necessary in many cases.  The British Thoracic Society (BTS) guidelines for community acquired pneumonia (CAP) recommend the following:

• Chest radiography should not be considered a routine investigation in children thought to have community acquired pneumonia. 
• Children with signs and symptoms of pneumonia who are not admitted to hospital should not have a chest x-ray.

These recommendations are based on two important facts.

• Children with clear clinical signs of CAP may have a normal CXR
• Children with abnormal findings on a CXR often do not have clinically significant CAP (2)

So when should we do CXR in children?

Let’s start with the times when CXR is not recommended routinely:

• Bronchiolitis not requiring admission to a critical care unit (PCCU)
• Episodes of asthma and viral wheeze (no matter how severe or whether it is the first episode of wheeze for that child) which are responding to treatment
• Community acquired pneumonia without atypical features and which responds to treatment within the first two days
• Most cases of cough without other features
• Chest pain in children

CXR is usually most helpful in children in these circumstances

• Severe exacerbations of asthma or viral wheeze which are getting worse despite appropriate treatment 
• Community acquired pneumonia which has atypical features or fails to respond to appropriate treatment
• Daily cough with any of the following features
• Lasting more than 8 weeks
• Progressively worsening over several weeks, esp. if moist cough
• Red flag features (daily fever, night sweats, weight loss)
• Known exposure to TB
• History consistent with inhaled foreign body

The other side of the problem is that there is no gold standard test for many of those clinical scenarios where CXR is not routinely recommended.  There is often poor correlation between clinical and radiological findings, but which is more valid?  For example if you take pneumonia in children and treat based on radiological findings versus clinical findings you will end up treating different children.  Clinical findings will be falsely positive and falsely negative just as radiological findings are.

Therefore we need to get a balance between clinical common sense and judicious use of CXR in children.  A simplistic approach which could be applied looks like this:

Whether a CXR is necessary or not is highly subjective.  Ask ten clinicians and you'll get ten different answers, due to the human factors.  It's a little like an umpire in a tennis game.  They're not right all of the time.

For this reason, in a major tournament tennis game, players are allowed to appeal.  However the players appeals are limited.  If they appeal against a decision and that appeal is upheld, they retain the number of appeals that they had before the appeal.  So wrong once, they can appeal again.  Wrong twice and they're out of appeals.

I suggest that clinicians should apply the same rules to the use of CXR in children.  Before doing a CXR, we should ask ourselves the question, "What would I do based on a purely clinical assessment?"  After doing a CXR, we should then ask, "Has the CXR added genuinely useful information to my clinical decision?"

Having a CXR result in a child which doesn't alter our clinical decision, or which dysfunctionally suggests a pathology in the absence of a congruous clinical picture should make us rethink our approach to our use of CXR.  If we're going to apply the Wimbledon CXR rule, when we get one completely normal CXR (or one with a non-descript small white fluffy patch which makes us want to give antibiotics when we wouldn't have done so before the CXR) we should think about more cautious use of CXR. If we get two, we should stop and re-read the rules.

Just as tournament tennis players don't have an unlimited number of appeals, we shouldn't think of CXRs as an unlimited diagnostic resource.  We should use them when they are most likely to change our game.

Edward Snelson
Unappealing Paediatrician
@sailordoctor

Disclaimer: If you turn the umpire off and back on, the number of appeals resets.

References

1. Hirsch, A. et al., Estimating Risk of Pneumonia in a Prospective Emergency Department Cohort, The Journal of Pediatrics, Volume 204, 172 - 176.e1
2. Virkki R, et al. Radiographic follow-up of pneumonia in children. Pediatr Pulm 2005;40:223e7.

Making the Right Judgement - a comprehensive 3D model for deciding what to do with each child with a respiratory presentation

In the previous post, I covered how best to make a diagnosis of lower respiratory tract infection (LRTI).  Anyone who has the pleasure of working with acutely ill children knows, the diagnosis is only a small part of what we do.  A big part of what we do is making that all important decision - home or hospital?

This decision is usually made up of several elements.  What is interesting is that the same principles can be applied to all of the major respiratory problems that we see, namely:

• Bronchiolitis
• Viral Wheeze
• Asthma
• Croup
• Pneumonia (LRTI)

Once one of these diagnoses has been made, the decision about whether to admit or manage at home is a huge one.  On the one hand, we don't want to admit children to hospital unnecessarily.  Apart from the inconvenience and stress to the family, there is a significant risk of adding insult to injury as so many children who attend hospital acquire additional infection.  On the other hand, we know that if a respiratory problem does deteriorate, it can do so quickly and catastrophically.  If there is a significant risk of a child going off, they should be somewhere that can respond appropriately.

In the majority of childhood respiratory illnesses, the treatment itself is not what requires the child to be in hospital.  It is no longer routine to have a chest X-ray and intravenous antibiotics for uncomplicated community acquired pneumonia. (1)  Many children who are admitted with pneumonia receive no investigations and are treated with oral amoxicillin and discharged when they show improvement.  Severe croup is often a waiting game.  Viral wheeze is usually treated with inhalers via spacer.  Babies with bronchiolitis are often observed while a team of expert paediatricians avoid the temptation to "try something" that research has proven to be pointless.  You get the picture.  These are the times that paediatrics is the art of masterful inactivity.  Believe me, that is harder than it sounds and is actually quite labour intensive when done properly.  The point is, they still need to be there, because these are the children who, if they got worse, would require escalation of treatment.

So if the need for hospital specific treatment isn't always the thing that determines the need for admission, what else is?  In illnesses that always need hospital treatment (e.g. Kawasaki Disease) the decision is made for you.  However in respiratory problems that can be treated in the community, the decision is mostly about risk assessment, which is never as simple as people make it sound.

Guidelines often imply that the assessment of a respiratory presentation is a simple matter of deciding severity or calculating a score.  I like an over-simplification as much as the next clinician, except when it doesn't work, which is fairly often.  Why isn't it that simple?  Because not a one dimensional assessment.  The good news is, it's not that complicated,  It's just 3D instead.

D1 - Severity

The first dimension of the assessment is to decide severity.  All acute respiratory problems, like chain coffees, come in small medium and large.  Deciding which presentation fits into mild moderate or severe is fairly intuitive and the same principles apply across the different diseases.

Severe makes the decision easy.  Severe needs to be treated in hospital for several reasons.  Severe is usually a set piece, and although severe can be terrifying, it's not usually a cause of decision fatigue.  That comes from deciding what to do with the rest of them.

In a previous post, I shared some thoughts on croup scores and severity.  You can read that via this link if it would be helpful.

Mild cases of croup, bronchiolitis, viral wheeze, asthma and LRTI are almost always best managed at home.  Almost.  Moderate cases can often go either way.

D2 - Risk factors

This means that other factors are involved in the decision.  Because we are assessing risk, we need to consider risk factors.  These, when applied to the severity of the illness literally multiply the risk of something bad happening.

As a rule, a risk factor alongside a moderate severity of respiratory problem is ore than enough to mandate admission to hospital.   That child with croup that you were thinking of sending home- I suspect that decision will be changed when you factor in the fact that they were born prematurely at 26 weeks.

What is slightly more complicated is how risk factors apply to the child with a mild presentation.  It's complicated because the presence of a risk factor does still ramp up the risk, but its a factor applied to a very small risk in the first place.  What's more, the same risk factors that apply to the presentation also apply to the risk of being in hospital.  An ex-premature baby with mild bronchiolitis could go off, but the risk is still small.  An ex-prem baby in hospital if they don't need to be is a risk all of its own.

The decision about what to do with a child who has a mild respiratory problem but also has risk factors is a difficult one.  It is a decision best made by an experienced clinician who understands the way that the particular risk factor interacts with the illness and knows the pitfalls associated with it.  If you're not sure, refer or discuss the case.  This may be a good opportunity for an experienced primary care clinician to share that decision with an experienced paediatician via a telephone consultation.

D3 - Red Flags

Finally, there are red flags.  Although independent of the apparent severity of the presentation, these features will usually mandate referral or admission.

A good example of a red flag feature would be a 4 month whose clinical examination is consistent with mild bronchiolitis.  If the accompanying adult says that the infant had an episode of suddenly becoming pale and floppy earlier that day, this should be treated as a warning sign.

Bringing those three dimensions together will give you the answer to the "home or hospital?" question.  It will also help the communication between primary and secondary care.  Referring a child with a respiratory problem, summarised as diagnosis, severity, risk factors and red flags is just showing off.  There's nothing wrong with that is there?

Edward Snelson
Dimensional Relativist
@sailordoctor

Disclaimer: I'm never sure which is worse: oversimplification or undersimplification.

References

1. Guidelines for the management of community acquired pneumonia in children: update 2011 British Thoracic Society Community Acquired Pneumonia in Children Guideline Group

Why Do Different Children Wheeze Differently? - Simple, but first you have to understand all of paediatrics (also simple)

When a child or young person has one or more wheezy episode, there are various possible causes.  The vast majority of paediatric wheeze is caused by bronchiolitis, viral wheeze and asthma.  It is easy to confuse these conditions, but clarity of diagnosis has real benefits when it comes to providing evidence based treatment.

We know that getting the diagnosis right isn't straightforward, possibly because there are no tests which reliably distinguish these entities from each other in children.  For example, evidence suggests that 50% of children diagnosed as asthmatic do not have asthma (1).  One knock-on effect of any diagnostic difficulties is that people make up rules for us.  "Asthma should not be diagnosed under the age of 5 years."   "Inhalers don't work under the age of 12 months."   These rules are meant to be helpful, but they are both wrong.  If you were only playing the odds, living by these rules would be the way to go, but clinical medicine is also about pattern recognition.  If it looks like a duck etc.

I think that it is possible to embrace the rules, while also knowing when to break them.  I believe that there is a simple model for understanding paediatric wheeze which fits into the probability model and the pattern recognition model.  It's fairly simple and all it requires is a good understanding of all of paediatrics.

Paediatrics isn't the art of learning 30,000 rare conditions.  Paediatrics is mostly about understanding what conditions affect children at different ages and how children respond to those illnesses.  That in turn allows us to recognise and treat appropriately wherever possible.  When it comes to infections and immune responses, unsurprisingly the immune system plays a big role.  Of course a child's immune system goes through several stages and each one dictates a different response to infection and allergens.

How does a baby fight infection?  In simple terms, they don't.  Inherited antibodies do most of the work for the first few months.  Few pathogens get past these antibodies and so the baby's own immune system does very little.  This has lots of implications.  Infections that do occur are unlikely to be common viral illnesses and whatever the pathogen, the baby will be at greater risk from that infection.  Even the recognition of an unwell baby is affected by their lazy immune response.  Temperature of 40C in a 7 day old?  Pull the other leg.

These maternal antibodies eventually run out.  The immune system has to learn and develop.  Older children, like adults have a complex and clever immune system which has stored a wealth of information about the pathogens in their environment.  This allows the older child to produce a response to infection that is not just complicated but sometimes over-complicated.

So how does a human survive in-between losing maternal antibodies and learning a more complex immune response?  In scientific terms, their immune system goes nuts.  You have seen it yourself: even with a relatively simple and uncomplicated viral infection, the younger child can have very high temperatures, various rashes and of course viral wheeze.  Other things that are common in this age group are quite possibly in part due to this exaggerated immune response - irritable hips and febrile convulsions.

These three ways of responding to infection align very nicely with the three entities that commonly cause wheeze at different ages in children.

So, the rules about age do have a solid basis.  Would you diagnose asthma when a six week old becomes wheezy?  Please don't.  Would you diagnose bronchiolitis in a 12 year old?  No.

Age alone does not give you the diagnosis since there is some overlap.  Thankfully, because each condition represents a different immune response, they each present with slightly different clinical features. As a result we can combine probability with pattern recognition.  The best bit is that the pattern recognition fits well with these three immunological stages of childhood.

What happens when you are a baby and a virus causes a respiratory tract infection?  In most cases, the answer is simply wetness.  Bronchiolitis is what you might expect from an immune system that has not yet fully woken up from its cocoon of maternal antibodies.  Bronchiolitis tends to slowly progress over days from cough and coryza to wheeze and suboptimal feeding, finally ending up with a variable degree of respiratory distress.  It progresses over days.  The severity and progression of these symptoms will vary from child to child, however the gradual onset is characteristic.  This is not to be confused with deterioration, which can be sudden, especially in high risk babies.

Viral wheeze by contrast tends to come on quickly, over hours rather than days.  This is because in viral wheeze is a different response to the same viral trigger.  In children between the ages of about 1 and 6, when the immune system sees a new virus, it tends to go a bit crazy.  One of the effects of this immuno-enthusiasm seems to be that that many children experience bronchospasm as part of that immune response.  So in addition to being able to tell which is more likely (bronchiolitis or viral wheeze) by the age of the child, the rapidity of the onset of the wheeze is a clue.

Why does it matter that we tell the difference?  These two different entities respond differently to treatment.  The slow development of inflammation and wetness in the airways that is bronchiolitis does not respond to bronchodilators while the bronchospasm of viral wheeze does.  This is probably the reason for the perpetuated myth that children under the age of one don't respond to beta-agonists.  They do, but only if they have bronchospasm (viral wheeze) as opposed to mostly wetness (bronchiolitis).

Finally, when your immune system moves from the "shoot first, ask questions later" mode into adult mode, asthma becomes the most common cause of wheezing in children and young people.  The trouble is that this isn't something that happens suddenly and it certainly isn't the case that there is a consistent age for this to happen.  Once again though, odds are very much affected by the age of the child.  Does the 8 month old have asthma?  No.  Does the 15 year old have episodic viral wheeze.  Almost certainly not.  Once again, the fact that the different entities represent different stages of immune system maturity translates into both probability and pattern recognition.  The 3 year old is probably having episodes of viral wheeze, but this will be confirmed by the fact that all episodes are precipitated by viral illnesses and the lack of interval symptoms.  The 10 year old probably has asthma and if this is the case they will be having episodes of wheeze not just when they get viral illnesses.

This explains the contradictions between all of the things that we know about asthma in children.  We are told that we shouldn't diagnose asthma under the age of five.  That rule works well from a probability point of view but not from a pattern recognition point of view.  What would you do if a 3 year old has a chronic cough and multiple episodes of wheeze that are not all provoked by viral illnesses?  I think that this child might be the exception to the probability rule.  Equally, in a 2 year old with chronic cough and no history of wheeze the temptation to diagnose asthma is a dangerous one given both the lack of  probability and the absence of a classic history.

Understanding the way that children respond to infection at different ages tells us a lot about where (what age) to look for each diagnosis and what to expect (the classic history) to find in order to confirm that diagnosis.  This allows us to maximise the chances of giving the most appropriate treatment, most of the time.

When there is a discrepancy, we need to be aware that probability and pattern have not agreed, and have a low threshold for rethinking.

Edward Snelson
Occasional rule analyst
@sailordoctor

Disclaimer: No-one understands all of paediatrics.  I mean really, who can explain why children will eat glue and drink air freshener but refuse to eat the food that you want them to eat?  That's why it's best to stick to the basics (like immunology) and leave the complicated stuff to the parents.

References

1. Ingrid Looijmans-van den Akker, Karen van Luijn and Theo Verheij, Overdiagnosis of asthma in children in primary care: a retrospective analysis, Br J Gen Pract 2016; 66 (644): e152-e157

Investigations in Bronchiolitis - Help a Brother Out

One of the things that a crisis should do is to bring people together.  As the UK's National Health Service experiences a winter that is bringing  it to it's knees, we should be more aware than ever that Primary and Secondary Care need to work together as a team so that we all come out the other end of this intact.  There are those in each camp that are so entrenched in the us-and-them mentality that this idea of teamwork is against  their very being.  If you think that General (family) Practitioners (GPs) are lazy idiots or you think that hospital doctors are arrogant and lack communication skills, I'm not sure that I've got anything to help you.  (Perhaps a hug?)  If you are willing to believe that we are all part of a team and that any divisions are both understandable and resolvable, read on.

The issues that cause division are (in my experience) usually due to misunderstanding and a lack of insight into the part that we play in creating these disparities.  The irritations that I cause my colleagues, whether in Primary or Secondary Care, tend to be completely unintentional.  Sometimes it can be what seems like the smallest thing and I have no idea of the impact it has on someone else.  That's why it's so important to talk to each other.

Let me describe an example: the seemingly simple act of requesting a chest X-ray for a baby with bronchiolitis.

Bronchiolitis is usually a set piece.  An infant, usually under 12 months old, gets inflammation in their airways during a viral respiratory tract infection.  This leads to a three to five day period of increasing symptoms that usually consist of cough, wheeze, difficulty feeding and increased work of breathing.  In practical terms, that might play out like this:

Monday - A three month old is snotty and coughing but well and feeding nicely.  Breathing will probably be normal at this stage.

Tuesday - The parents have now noticed some noisy breathing and that feeding isn't as good as it normally is.  like many people in these circumstances, they seek a medical opinion and so go to their GP.  They are seen and the diagnosis of bronchiolitis is explained.  The clinician advises frequent small feeds and gives safety-netting advice for what to look out for in case this child becomes one of the very small minority who develop breathing or feeding difficulties that require support as an inpatient.  In keeping with NICE guidelines (1), they do no tests and give no treatments.

Wednesday - The parents have noticed a slight worsening of the feeding and are unsure about whether this is bad enough to need something to be done.  They hold off doing anything during the day but when their baby refuses an evening feed they take their precious bundle to the local emergency department.  There the child gets a thorough assessment.  Clinically the infant is well hydrated and although they have wheeze and mild recession they are looking happy and have oxygen saturations of 95% in air. Despite the earlier feed refusal, they now take 100 mls of milk. The assessing clinician hears a few crackles in the chest and decides to do a chest X-ray, just to be sure that today's worsening symptoms are not due to a bacterial pneumonia developing.

When is it necessary to do a chest X-ray for babies with bronchiolitis?

There are many possible complications of bronchiolitis.  In theory, these should be apparent on a chest X-ray.  There are also conditions that mimic simple bronchiolitis, most notably congestive cardiac failure.  So, a chest X-ray seems a sensible thing to do to add value to the assessment.  Except that it doesn't, for two main reasons.

These are the reasons why a chest X-ray doesn't add value to the assessment of a typical presentation of bronchiolitis:

• There is always something to be seen on the X-ray.  If you are looking for normal, you are unlikely to find it.
• If the infant has bronchiolitis, that is enough explanation for their clinical condition.  If they had a complication such as lobar pneumonia as well, you would't be doing the chest X-ray to see if there is a problem, you'd be doing it because the child is seriously unwell.

Coming back to our little one with bronchiolitis, let's assume that the chest X-ray shows what it always shows in bronchiolitis - something of uncertain significance.  There will be a little fluffy shadow somewhere due to the mucous plugging and atelectasis that is part and parcel of bronchiolitis.  Often, there is something to be seen at the right heart border (or as a wise radiologist once redefined for me: "the area of radiological romance") which may or may not be something.  Once seen, it is very difficult not to feel the need to treat for possible bacterial infection.  This brings me on to the next few reasons for not doing a chest X-ray.

Doing a chest X-ray in bronchiolitis is associated with increased antibiotic prescribing rates.  Bacterial superinfection in bronchiolitis is rare and is usually clinically apparent.  Bronchiolitis is reason enough to have respiratory symptoms.  If a baby also develops pneumonia, they are usually quite unwell and have a marked degree of distress.  So, following that logic, for our baby the antibiotics are simply unnecessary, in which case they may do harm.  Since one of the problems that comes with bronchiolitis is feeding and hydration, why give these babies a gastric irritant?

Finally, there is a second victim here: the clinician who saw the baby on Tuesday.  Despite sterling work by the GP, the parents are likely to believe in retrospect that they were given a poor service.
All the evidence is there:

• The person that they saw in the community did nothing and their child became worse.  
• The experts in the hospital did a test which showed that their baby needed antibiotics.
• Antibiotics were given and eventually the bronchiolitis got better. 

Why didn't the GP do something when we went the first time?

Of course both clinicians in this story were trying to do their best for the patient.  Neither of them had anything on their mind other than trying to ensure the best outcome for the child. There was no disrespect intended and no one wanted to cause anyone any problems.  We are all just trying to get through the day and to keep our patients safe and well.

Thankfully, it turns out that in bronchiolitis, keeping your patient safe and well is probably best done without the use of chest x-ray and antibiotics.  So, we in Secondary Care can help our colleagues in Primary Care out by making the assessment that needs to be made: in or out (of hospital)?  That decision is made on clinical grounds and if they need to be admitted, a chest X-ray may be useful.  Maybe.

Edward Snelson
Vice President of the Guild of Doing as Much Nothing as Possible
@sailordoctor

Disclaimer:  I did a chest X-ray for bronchiolitis once.  There was a white patch at the right heart border but it turned out to be tippex on the screen.

Reference

1. Bronchiolitis in children: diagnosis and management, NICE guideline [NG9] Published date: June 2015

It's Not Easy Being Wheezy - about antibiotics and wheezy kids

In my formative postgaduate years as a doctor, I was told by more than one mentor that antibiotics were a good treatment for children who were wheezing. This advice was given by various people at different times and whether this was bronchiolitis, viral wheeze* or an exacerbation of asthma, the principles seemed to be the same. The logic is sound - we know that infection triggers all three, and we can never be certain of the infection being a straightforward viral episode.  That was how it was put to me anyway.
*If you are unsure about the difference between viral wheeze and bronchilitis, follow this link for an explanation.

I no longer believe in this strategy as a treatment option for wheezy kids, and this is why:

It's not easy being wheezy.  Children with tight lower airways are up against it but often cope extremely well with their bronchospasm or their bronchiolitis.  I am constantly delighted by the ability of these children to be cheerful despite quite significant breathing difficulty.

It's even worse to have a bacterial lower respiratory tract infection.  As well as the breathing difficulty that comes from the loss of functioning lung, there is the tiring effect of the illness.  Having pneumonia is unpleasant and often exhausting.  It would be unusual to see a child who was cheerful and well despite a bacterial lower respiratory tract infection.

Now imagine combining the two.  Doesn't look good does it?  Children with bronchiolitis and viral wheeze cope with the difficulties of wet or constricted airways because they are systemically well.  Add the lethargy of bacterial infection to this and you go from a child who can compensate to one who cannot.  In short, you won't think "maybe there's a bacterial LRTI as well as the bronchiolitis or viral wheeze."  You'll know it.

Evidence from research backs this up.  The Cochrane review of antibiotics for bronchiolitis concluded that there was no benefit from antibiotics. (1)

You could say, what's the harm in trying antibiotics?  There are many reasons why unnecessary antibiotics might be harmful and none of these are to do with drug resistance.

So, it's time to do away with the idea that antibiotics have a role in treating well children with bronchiolitis or viral wheeze.  I believe that you'll know the children who need antibiotics because they will be properly unwell.

Edward Snelson
Antibiotic Guardian of the Galaxy
@sailordoctor

Disclaimer:  Secretly we all know that antibiotics do treat viruses, but if you tell anyone, you'll be removed from the Magic Circle.

Reference

1. Farley R et al, Antibiotics for bronchiolitis in children under two years of age, Cochrane database of systematic reviews. 2010

The Well Covered Wheezer

Guidelines almost always dedicate themselves to 'what to look out for'- the red fags and risk factors.  Often, we go to a guideline in order to learn about a condition, only to find that we should be afraid, very afraid.  I think that the tendency for the glass-half-empty factor in guidelines is almost certainly due to the understandable desire to err on the side of caution.  When you are writing a guideline, you are very aware that if (when) a patient has a bad outcome, the guideline's recommendations will be critiqued.

However, I don't want my doctor to intentionally err at all. To be honest, the error being on the side of caution is very little consolation.  Unnecessary tests, treatments, referrals and admissions are not what I want.  I want my clinician to be thoughtful and careful, but courageous, not risk averse.   I believe  that calculated risk is a necessary part of practicing medicine well, and so struggle with guidelines that give us the impression that we have to follow a certain pathway even when our instinct tells us that this is not needed.

Of course, I know that many of you will now be thinking, “Guidelines are just guidelines.  You don’t have to follow them.”  While this is of course a true statement, try telling this to a clinician who has been to court regarding an adverse outcome.

I don't want to return to an era bereft of guidelines.  That was no fun at all.  Someone else knew what you were supposed to do, most of the time.  It was your job to guess what was expected of you and then find out afterwards if you were right, rather that to be told beforehand.  However, we need to be aware of the negative effects of guidelines, so that we can protect against these.  (1,2)

I do feel that the guideline era has taken some of what used to be taught and allowed this to drift into mythology.  So, in the interest of history, I thought that I would explore what the guidelines often miss out – the signs that are reassuring.  When marking some assignments for the Primary Care Paediatrics course at Sheffield Hallam University, I was delighted to find the oldest reference that I have ever seen in one of these submissions.

Cassell’s Household Guide to Domestic Medicine (1886) - “…on the minutest air-tubes the cells of the lungs are placed… inflammation of these tubes is one of the most fatal diseases in our climate…The child is quickly bereft of its usual liveliness… the breathing is quick and the nostrils expand more or less… All these symptoms are worse if they occur in delicate children…”(3)

The first thing that struck me about this was that in Victorian Britain, the pathophysiology of bronchiolitis was already known.  The second was that they recognised that scrawny babies with bronchiolitis were the ones to worry about.  This brings me onto the well covered wheezer.

In the days before guidelines, I learned paediatrics by trial and error with a degree of question and answer.

Me: “This child is very wheezy.”

Consultant:  “They’ll be fine.  They’re a fat, happy wheezer.”

Me: “So because they’re a bonnie baby and smiling, they’ll be fine?”

Consultant: “Pretty much.”

I don’t know of any research demonstrating the protective benefits of an extra pound of subcutaneous fat when suffering with bronchiolitis.  What I can tell you is that 20 years on, I’ve never had cause to feel misled by this conversation.  That is partly because I leaned the difference between red flags and those that were more of a blood orange colour.

I would say that it is only the 'significant tachypnoea or recession' which could be negated by other reassuring factors such as being well covered and cheerful.  I also think that this is probably self fulfilling: children with the other red flags are too significantly affected to actually have any reassuring features.

What is also interesting is that, in a straw poll of ten junior doctors, none had heard the term ‘fat happy wheezer.’  This is not down to modernity either.  None of the doctors in question had heard it said that habitus was worth considering when assessing a child with bronchiolitis.  I put this down to an overemphasis on red flags and risk factors, without justice being given to reassuring signs.

So, I am going to appeal to two groups of clinicians to help restore balance to The Force:

Firstly – all you experienced, common sense clinicians, please comment below and let me know what other things are reassuring signs which might be unproven but tell you not to be so worried.

Secondly – all you academics, please research these things and get us the evidence to back up what we all know to be true.  After all, this stuff has been known for 130 years now. It’s time we proved it.

Edward Snelson
Alternative Medical Factivist
@sailordoctor

Disclaimer - I followed a guideline once, and I liked it.

Thanks to Fiona Hardman for the Cassell's Household Guide reference

References

1. Bowen et al, The transition to clinical expert: enhanced decision making for children aged less than 5 years attending the paediatric ED with acute respiratory conditions, EMJ 2015
2. Green et al, Admission to hospital for bronchiolitis in England: trends over five decades, geographical variation and association with perinatal characteristics and subsequent asthma, ADC, 2015
3. Cassell’s Household Guide to Domestic Medicine (1886), Diseases Incidental to Children, p84

If you can't decide between turkey and goose... Pertussiolitis and other animals - when a child has noisy breathing

Recently I learned a good way to find the answer to a question.  It happened like this-

On a walk in Sheffield I saw this strange bird:

Unable to find this creature described in a ‘Birds of Britain’ book, I posted the picture to Facebook and commented that (to me) it looked like a cross between a turkey and a goose.  Most other Facebookers were similarly unfamiliar with the species but within a short period of time, I received a response from my niece who declared the bird to be a Muscovy duck.  After quickly confirming this to be true, I asked how she recognised this bird which is not native to the UK.  The response that came back was simply that she had searched the internet for "birds which look like a cross between a turkey and a goose". 

Boom.

I had the chance to complete this lesson, for myself in a clinical context, shortly afterwards when faced with another unfamiliar animal, this time in the form of a baby with an ambiguous presentation.  The child had developed a cough and feeding difficulties and had now become wheezy.  Preemptively, my diagnostic centres had skipped forward to the disease that I thought I merely needed to confirm: bronchiolitis.   This mental process was interrupted by a cough from the child, and what a cough it was.  It went on and on and on…  At the end of the period of coughing, the child’s face was properly red. The mother informed me that more often than not a spectacular vomit followed these paroxysms of cough.

With the new possibility of whooping cough suggesting itself, I examined the child with a new mission: confirm findings that are consistent with pertussis infection.  I was therefore, properly annoyed to find a wheeze which I felt was more in keeping with bronchiolitis.  Faced with this puzzle and remembering my niece’s methods, I asked the internet and found that, while not a typical feature of pertussis infection, wheeze has been well described in a large number of cases of children with whooping cough. (1)

This case reminded that, as primary care clinicians, we don’t really diagnose infections- we diagnose syndromes.  Bronchiolitis, for example, is not RSV infection.  Bronchiolitis is a syndrome of wheeze, poor feeding and cough which can lead to severe respiratory distress, apnoea and feeding or respiratory failure.  RSV is one possible cause amongst many untreatable viruses.

Similarly, despite what I was once taught, croup is not caused by parainfluenza virus.  Any virus can cause the upper airway swelling that leads to barking cough, possibly stridor and varying degrees of respiratory distress.

Just to keep me on my toes, children seen to present from time to time with features of multiple syndromes.  The most common bedfellows are croup and viral induced wheeze.  When faced with a child who has a barking cough and a wheeze, one initially questions whether the noise is in fact a stridor (and rightly so).  If it is a wheeze, then it is a wheeze.  If the child has both croup and viral induced wheeze, ther is no point trying to limit the diagnosis.  Just get on and treat both.  It occasionally causes a bit of confusion if the child needs admission.  I think that some junior doctors take the referral of a child with the diagnosis of viral wheeze and croup together to be a sign of uncertainty, or perhaps dementia.

I would suggest that perhaps wheeze is not a feature of whooping cough but that it is possible for a baby to have bronchiolitis at the same time as whooping cough, both caused by pertussis infection.  It doesn't really matter though, since the cause of the infection is only of interest if it can be treated, or transmission prevented.

There are so many infectious causes of noisy breathing in children. Here is a simple guide to what’s what and what to do about it:

Many thanks to my niece for teaching me what the internet is for.

Edward Snelson
Ornithopathologist
@sailordoctor

Disclaimer: I take full credit for inventing the use of evidence based medicine in the consulting room.

Reference:

1. Taylor Z.W. et al, Wheezing in children with pertussis associated with delayed pertussis diagnosis, Pediatr Infect Dis J. 2014 Apr;33(4):351-4.

Acknowledgement: This is a slightly different version of a post which I wrote for the Network Locum Blog earlier this year.

Why bronchiolitis doesn't get better with inhalers and how understanding "why?" is better than "do that!"

There was interesting debate this week about using inhalers for bronchiolitis.  The interesting features included how heated it became (there was mild name calling and much "prove it" involved, rated PG) and how confident people were in expressing their views on social media about their differing clinical practice.  (Take it from me that you should be fairly sure of yourself before you put something out onto the interweb.)  To me what was most interesting was that the views, despite being polar opposites, where seen as fact.  I am going to assume that all involved want to practice the best possible medicine, but someone must be wrong mustn't they?

What do the guidelines say?  The American Academy of Pediatrics and the UK's National Institution of Clinical Excellence along with other institutions, have produced guidelines in the past few years, specifying that beta agonists and ipratopium should not be used, so why are such debates still happening?  I think that there are a few reasons.  One of these is that for medics, knowing what to do is not as powerful as knowing why, especially when it comes to changing practice.  For me, understanding a disease is much more effective as a learning process than being told, "This is the disease and this is the treatment."   I suppose it is because I already understood the reason why I was doing what I was doing (even if the understanding was flawed), so a diktat is not as powerful a persuader as a new and better understanding.

There is a perpetuated myth regarding beta-receptors and infants.  This myth comes from early studies that failed to find evidence of beta-receptors in infants.  Since then, (as early as 1987) research of better methodology (3) has proven that these receptors are there from birth.  The myth persists because (just as the news reports plenty of crises but not so many resolutions) we are often told things, but rarely does anyone untell us something.

Perversely, the beta-receptor folklore has done us no favours when it comes to trying to understand bronchiolitis and viral wheeze.  The uncertainty created by this myth makes clinicians think that a lack of beta receptors has caused the lack of response to salbutamol.  In fact, the child would respond just fine if only they had bronchospasm.

In bronchiolitis, there is no bronchospasm so salbutamol does not help.  In viral wheeze, ipratopium is a poor treatment and the old myth about ipratropium leads some to believe that ipratropium is the first line treatment for this age group when what they really need is plenty of salbutamol if they really do have bronchospasm.

When discussing the management of wheeze in infants, I often get the impression that people believe that bronchiolitis is just what you call viral wheeze in a child under the age of 12 months.  In fact this is not true.  Bronchiolitis is a separate entity, with different histopathology and a unique clinical pattern of illness.  There is a gradual unset of symptoms, peaking at day 3-4 and beginning to resolve at day 7-10.  Doesn't sound very spasmy does it?

Of course the confusion arises from the fact that both bronchiolitis and viral wheeze are caused by a viral illness.  They can both occur in a child around the age of 12 months old and they cause similar symptoms.  There is however a subtle but helpful difference in the way that they present.

The reason for this difference is a difference in mechanism.  While bronchiolitis and viral wheeze share a cause, the pathology is different because the effects on the airways are different.

I suppose that since it is unrealistic to think that all uncertainty can be removed, the question remains, what is the harm in trying a bronchodilator in all every case, just in case?  Here are a few possible reasons why it is going to make things worse if it isn't going to make things better:

It's always difficult when two illnesses have so much overlap, but there are genuinely good reasons to avoid unnecessary treatment for bronchiolitis.  Hopefully understanding why bronchodilators don't work helps the thinking clinicians to decide for themselves, rather than just being told what to do by guidelines.

Edward Snelson
Mytharchivist
@sailordoctor


Disclaimer:  I would like to express my appreciation to the children who allowed me to perform lung biopsies on them during their wheezy episodes.  Science thanks you.


References

1. Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis, American Academy of Pediatrics, October 2014
2. NG9 Bronchiolitis in children: diagnosis and management, NICE, June 2015
3. A Prendiville et al., Airway responsiveness in wheezy infants: evidence for functional beta adrenergic receptors, Thorax. 1987 Feb; 42(2): 100–104.