Category Archives: Respiratory

Asthma

Common, General paediatrics, OPD, Respiratory

See BTS/SIGN/NICE 2025 guidance on asthma,  asthma prevention, asthma and obesity

FeNO is expensive and available in only a minority of GP practices and hospital services.  Requiring it means GPs can no longer make diagnosis themselves.

Spirometry results in most primary care patients with asthma are normal!

Spacer best for everyone! Orange aerochamber is small mask, up to 18 months, yellow is 1-5yrs. Green is 5+, blue is adult. You can get blue with mask, not green.

200 doses in an MDI.   2 puffs BD exhausts an MDI in 50 days. Multidosing 5 puffs 4hrly will exhaust it in 6 days.

Growth Restriction

Children who use inhaled steroids for asthma grow slower than their peers in the first year of taking the medication, by about half a centimetre per year. Metanalysis of 25 trials, various types of steroid.  Seems to be most obvious in initial year of treatment.  Only 1 study followed children into adulthood – budesonide, used for average of 4 years – reduction in final height of  1.2cm (Kelly, PMID 22938716).

Should therefore be prescribed at the lowest effective dose. Cochrane 2014 found significant difference between low dosing (50-100 Clenil equivalent) and medium dosing  of 0.2cm per year but noted that the  majority of trials did not report height data.

However, the small effect on growth needs to be weighed against the proven benefits of these drugs in controlling asthma, and ensuring children’s lungs grow to their full capacity.   Undertreated asthma is much more likely to have a harmful effect on a child’s development than a small reduction in growth.

Newer Therapies

Xolair=Omalizumab, monoclonal vs IgE. Subcut, 2-4 weekly, for age 6+ where conventional therapy not working.  Other criteria are total igE >30, positive tests for aeroallergens, FEV1<80%.

Airsonett is evidence based, temperature controlled laminar flow system for bedroom. Noisy!

Management

See National review of asthma deaths.  Recommendations include:

  • Refer specialist if >=2 courses oral steroids within 12 month period
  • Follow up after every ED/OOH attendance
  • Hospital follow up after every hospital attendance
  • Annual inhaler technique check
  • Personal asthma plan for everyone

See MyLungsMyLife.org website for self management.

Asthma prevention

Common, General paediatrics, Respiratory

Atopy is not a single phenotype, the idea of an “atopic march” from infantile eczema through food allergy to asthma and rhinitis is way too simplistic. Early interventions have been disappointing. Curiously, food allergies and eczema often improve through childhood – this seems less common with asthma.

There are different risk groups.  Environmental exposure to allergens and microbes in early life is one factor.  Farm environment protects (exposures and/or dietary).

Most studies show dog ownership protective. Weaker evidence for cats. House dust mite sensitisation in early life predicts asthma in school age.  Primary prevention of HDM sensitisation has conflicting evidence – Isle of Wight study showed mite avoidance prevented sensitisation and asthma; Canada study showed effectiveness but Dutch study did not.  Manchester study reduced early wheezing but had higher rates of sensitisation. Australian study no effect overall but depended on age.

Reduced bacterial diversity is a risk factor for asthma and atopic wheeze – certain bacteria esp bacteroides and firmacutes seem to be protective.

Viruses also play a role.  RSV is associated with later asthma regardless of existing atopy or not, although perhaps not with asthma persisting into adulthood; rhinovirus wheezing in first 3yrs is similarly associated with persistent wheeze, especially in atopic persons. So impact of more RSV and other vaccines could be fascinating.

Heritability of asthma accounts for less than 50% of patients so gene-environment interactions are at least as important.  A gene has been found that is associated with early childhood asthma with severe exacerbations (CDHR3). TSLP gene on chromosome 5q22 encodes for a master regulator for TH2 processes. But another well recognised gene region on chromosome 17q12-21 (including ORMDL3 and GSDMB) seems to be involved in airway dysregulation after virus infection, rather than allergy.

Increasing evidence that respiratory health is influenced by parental exposures that occur long before conception. The strongest evidence relates adolescent tobacco smoking and overweight in future fathers to increased asthma and lower lung function in their offspring, supported by evidence on parental preconception occupational exposures and air pollution.  Antenatal and postnatal (passive) smoking important. Role of breast feeding vs formula still controversial.

No evidence for asthma preventer treatment as an early intervention – cf JIA and other inflammatory conditions.

Grass immunotherapy for rhinitis in children reduces the incidence of later asthma and need for asthma medication. Presumably house dust mite immunotherapy would help too? HDM antigens have allergenic but also endotoxin and enzymatic effects! Jurgen’s study of HDM SLIT in infancy found reduced sensitisation (to anything, but def HDM – but only 11% difference and active group had more pets…); at 3 yrs, no difference in clinical outcomes, unfortunately – in fact, more wheeze…

Spanish RCT of oral bacterial extracts (6 different ones for 6 months) significantly reduced number of wheeze episodes (40%) for up to 1 year. Animal experiments have already shown that oral administration of bacterial extracts prevents bronchial hyperreactivity.

We should therefore encourage less Caesarean sections, more breast feeding, less antibiotic use, more green spaces, more “natural” food preparation and distribution (ie less plastic!).

[PAI 2023]

The GINI study

Allergy, General paediatrics, Immunology, Nutrition, OPD, Respiratory

German study from 1998.

Some potential benefit from using hydrolyzed formula in terms of preventing allergy.  The relative risk for the cumulative incidence of any allergic disease in the intention-to-treat analysis (n = 2252) was:

  • 0.87 (95% CI, 0.77-0.99) for partially hydrolysed whey-based formula (pHF-W),
  • 0.94 (95% CI, 0.83-1.07) for extensively hydrolysed whey-based formula (eHF-W) eg Pepti, and
  • 0.83 (95% CI, 0.72-0.95) for extensively hydrolysed casein-based formula (eHF-C) eg Nutramigen compared with standard cow’s milk formula.

The corresponding figures for atopic eczema/dermatits (AD) were 0.82 (95% CI, 0.68-1.00), 0.91 (95% CI, 0.76-1.10), and 0.72 (95% CI, 0.58-0.88), respectively.

In the per-protocol analysis (ie where patients stuck to protocol) effects were stronger (0.49 for eczema at 1yr). The period prevalence of AD at 7 to 10 years was significantly reduced with eHF-C in this analysis, but there was no preventive effect on asthma or allergic rhinitis.

[J Allergy Clin Immunol. 2013 Jun;131(6):1565-73. doi: 10.1016/j.jaci.2013.01.006. ]

Cochrane review 2009 biased towards GINI data.  Since then big Melbourne study (MACS) not in favour; per protocol analysis for eczema at age 1 yr did not show any benefit (0.55-1.93).

Even with GINI, NNT could be as high as 80!

[http://onlinelibrary.wiley.com/doi/10.1111/pai.12138/full]

15 yr follow up of GINI study – between 11 and 15 years,

  • prevalence of asthma was reduced in the eHF‐C group compared to CMF (OR 0.49, 95% CI 0.26–0.89)
  • cumulative incidence of atopic rhinitis was lower in eHF‐C (risk ratio (RR) 0.77, 95% CI 0.59–0.99]) and the AR prevalence lower in pHF‐W (OR 0.67, 95% CI 0.47–0.95) and eHF‐C (OR 0.59, 95% CI 0.41–0.84).
  • cumulative incidence of eczema was reduced in pHF‐W (RR 0.75, 95% CI 0.59–0.96) and eHF‐C (RR 0.60, 95% CI 0.46–0.77), as was the eczema prevalence between 11 and 15 years in eHF‐C (OR 0.42, 95% CI0.23–0.79).
  • No significant effects were found in the eHF‐W group on any manifestation,nor was there an effect on sensitization with any formula.

[Allergy 2016; 71: 210–219. http://onlinelibrary.wiley.com/doi/10.1111/all.12790/abstract]

National Review of asthma deaths

Common, General paediatrics, Respiratory

2014 Report (adults and kids) finds that routine asthma care, management of previous and final attacks is generally poor, but particularly for children cf adults.

Almost half did not seek medical help before death. 10% deaths within 1 month of discharge from hospital for asthma. Many being treated for mild/mod asthma, but review suggested prob poorly controlled severe asthma. Widespread over reliance on reliever inhalers and underuse of preventers. Overall 39% had used more than 12 blue inhalers in the year before death. 80% of deaths did not get 12 preventer inhalers in the previous year. Nearly half had not had an asthma review in previous year.

Poor follow up of previous severe attacks (but only about 20% had been in A&E in the previous year).

Delays in primary and secondary care in about a 1/3 of final attacks.

In 93% children and young people, one or more avoidable factors relating to patients, their families and their environment: eg exposed to smoke or smoked,  allergy,
Poor recognition of risk of adverse outcome from asthma.

Recommendations

Any patient prescribed more than 12 relievers in a year should have urgent review. Follow up should be made after every ED attendance for asthma. Every hospital discharge should have hospital outpatient follow up.

Should have personal asthma action plan (PAAP).

Better education on when to use asthma medication, recognise poor control, how/when to seek emergency advice.

For parents/patients

Triple A online test!

See GP within 48hrs of discharge.

Associations with depression and anxiety. Obesity mentioned.

Mycoplasma pneumonia

Infectious disease, Respiratory

Most common bacterial cause of pneumonia in children requiring hospitalisation (Clin Infect Dis 2019) – relatively older children (5+ yrs), more likely to have had recent antibiotics but otherwise clinically indistinguishable.

Studies have indicated that the prevalence of M. pneumoniae in the upper respiratory tract (PCR) is similar among asymptomatic, healthy children and children with a symptomatic respiratory tract infection!  Current diagnostic procedures for M. pneumoniae are unable to differentiate between bacterial carriage and infection!

Note rapid worldwide emergence of macrolide-resistant (MRMP) isolates.

Meyer Sauteur PM; van Rossum AM; Vink C.  Current Opinion in Infectious Diseases. 27(3):220-7, 2014 Jun. PMID UI: 24751894

Influenza – treatment

General paediatrics, Infectious disease, Respiratory

Oseltamivir and Zanamivir licensed for treatment and the former also for post-exposure prophylaxis.

Cochrane review 2014 found little evidence of benefit.  But this was based on community studies in healthy populations.

“Use of neuraminidase inhibitors in influenza” [October 2015, Academy of Medical Sciences] indicates that the use of antivirals can be beneficial in certain situations, but of limited use in others. Additionally, a recent review “Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza – review of recent systematic reviews and meta-analyses” August 2017, European Centre for Disease] supports use as treatment and prophylaxis.

UKHSA therefore recommends:

“Complicated” influenza defined as

  • requiring hospital admission,
  • signs of LRTI eg resp distress, chest signs
  • CNS signs
  • Worsening of underlying medical condition

Risk factors include:

  • infants under 6 months; 
  • neurological, hepatic, renal, pulmonary and chronic cardiac disease ; diabetes mellitus;
  • severe immunosuppression (includes prednisolone r≥2mg/kg/day for ≥1 week);
  • morbid obesity (Z score BMI 3.33 or higher).

Oseltamivir (Tamiflu) PO or NG is first line, unless severe immunosuppression and A(H1N1) variant prone to resistance dominant – then zanamavir.

  • Start treatment within 48hrs, do not wait on lab confirmation of diagnosis.  May still be benefit in life threatening illness when started up to 5 days after onset. Rule is within 36hrs if child and zanamavir.
  • should NOT be used in otherwise healthy patients but can be considered if felt to be “at serious risk of developing complications”.
  • Test for resistance if no response after 5 days of treatment.

Presumes flu-like illness and circulating influenza, CMO publishes advice when surveillance levels cross threshold.  Highly virulent strain would change things, of course. Further details including use of anti-virals at HPS.

Oseltamavir dose is twice daily for 5 days. Oral only, capsules can be opened and added to something sugary (very bitter).  Liquid preparation available but limited supply, prioritise for infants.  Give by NG if necessary.  Licensed for treatment at all ages now, prophylaxis only over 1 yr.  Diarrhoea and vomiting are the only significant side effects.  

The earlier it is started the better: starting within 12 hours reduced duration of illness by 3 days, start within 48 hours and only 1 day benefit. 5% of childhood infections will become resistant whereas this is unusual in adults, probably due to kids having higher viral loads in primary infection. Consider resistance if no benefit after 5 days treatment.

Zanamivir used for adolescents 12 years and older – taken again twice daily for 5 days by diskhaler (age less important than ability to use device!). No resistance, very low rate of side effects (wheeze!). Zanamavir is preferred in severely immunocompromised AND (probable) A(H1N1)pdm09 disease, as resistance is higher . Unlicensed IV form of zanamavir is available on compassionate named patient basis.

[Antiviral PHE guidance]

Prophylaxis

For prophylaxis, vaccination best!  But consider using anti-virals (NICE recommendations) for post-exposure prophylaxis with Oseltamivir where:

  • 13yrs or older
  • Have a risk factor, as above
  • Influenza A or B is circulating, as above
  • Present within 48hrs of close contact exposure
  • Have not had flu vaccine for this season, or too recently for it to have been effective (within 14 days), or the wrong type, or have a condition that means vaccine may not be fully effective, or localised outbreak eg care home

Dose is once daily for 10 days. Treatment for up to 6 weeks might be required during an epidemic.

Other comments

Amantadine not recommended – targets M2 protein, only effective against type A influenza, rapid resistance and side effects common.

2 adolescents in Japan have committed suicide while on oseltamavir, plus there have been a number of other neuropsychiatric reports.

Peramivir is IV preparation with marketing authorization in EU, not yet available in UK.

Wheeze

Common, General paediatrics, Respiratory

US and elsewhere use “bronchiolitis” to mean wheezing illness!  So beware definitions in studies.

Early aeroallergen sensitization predictive of ongoing symptoms and loss of lung function at school age, but does not predict response to treatment with inhaled corticosteroids (ICS)!

European Resp society task force diferentiate Episodic Viral Wheeze (EVW) from Multiple trigger wheeze (MTW) viz exercise, smoke, allergens.  Children may change categories over time.  Guides treatment.  But note that few RCTs have used this classification, and tend to conflate.

MTW is associated with more airflow obstruction, and the pathology (eosiniphilic inlfammation and remodelling) similar to asthma.  Eosiniophilic inflammation not seen in EVW.

Several clinical indices which attempt to predict future asthma – PPV generally under 50%.  Kids with EVW only have no increased risk of respiratory symptoms once they reach age 14.

No evidence that early ICS (intermittent or continuous) affects progression of disease.  [N Engl J Med 2006;354:1985-97 PMID 16687711]

Parental smoking linked to wheeze, asthma, bronchitis and nocturnal cough, with mean odds ratios all around 1.15, with independent effects of prenatal and postnatal exposures for most associations (PATY study (Pollution And The Young), n=53 879 children from 12 cross‐sectional studies).   “Not in front of the children” does not protect from effects [Jenny Pool, Cambridge – Thorax 2012;67:926]: 88% of children from families where parents only smoke outside still have detectable urine cotinine.  Nicotine levels in household dust and on surfaces is at least 3x higher in homes where parents smoke indoors, but still 5-7x higher in homes where parents smoke outside cf non-smoking houses [Tob Control 2004;13:29-37 doi:10.1136/tc.2003.003889].  Air pollution increases vulnerability to preschool wheeze, but no specific advice on individual exposure.

PREEMPT study of intermittent montelukast (1 week with onset of URTI) for EVW vs placebo reduced unscheduled consultations for asthma, days away from sc hool/nursery, parental time off work.  [Australia, Am J Respir Crit Care Med. 2007 Feb 15;175(4):323-9.] Similar findings from a US study, but not supported by much larger WAIT study, 3 way study of intermittent vs continuous montelukast vs placebo [Nwokoro, Lancet Respir Med. 2014 Oct;2(10):796-803. doi: 10.1016/S2213-2600(14)70186-9].  But “5/5 ALOX5 promoter genotype might identify a montelukast-responsive subgroup”? Discontinue when child is better, not after specified number of days!

Cochrane supports intermittent ICS for wheeze, but only due to small studies with unlicensed doses eg fluctic 750mcg BD!  No studies of combined ICS/montelukast.

No evidence for prophylactic continuous ICS, but studies looked at mild rather than severely affected children.   Could be tried if repeated hospital admission, in case interval symptoms underappreciated!  Beware growth suppression, review and wean/stop if able.

Hospital study of pred vs placebo (n=687) found no benefit!  SImilar study in primary care.  SO should not be automatic, esp when anticipated duration of admission less than 24 hours.

No evidence for treatment plans for preschool wheezers!

BMJ 2014;348:g15 Andrew Bush

Allergic Rhinitis

Allergy, General paediatrics, Immunology, Respiratory,

Under-recognized, particularly when chronic blockage (without itch/sneezing) rather than sneeze/discharge. Late phase reactions involving Eosinphil induction by T cells tends to produce chronic swelling and non-specific irritability eg cold air. Nose problems impact with everything connected eg eyes, sinuses, middle ear, lungs. Differential is wide eg CF/PCD, deviated septum, polyps.

ARIA= allergic rhinitis in asthma report (WHO).

Alpha 1 Antitrypsin deficiency

Gastro, General paediatrics, Genetics, Respiratory,

Similar incidence to CF in white populations. Protease inhibitor (PI), counteracts neutrophil elastase. Alleles include PiZ (defective), PiM (normal), PiNull (non functioning). Protein phenotype then described as Z, M, MZ, or None

  • Double Null – very high risk of COPD but no liver disease!
  • ZZ have high risk of COPD and liver disease.
  • SZ also seen, risk of COPD.

The risk of emphysema is increased in males, in asthma and especially in smokers.

PiMZ genotype does not appear to predispose to chronic liver disease (in case control study). On the other hand, patients with decompensated liver disease (of any cause) were significantly more likely to have PiMZ, and particularly in HCV or NAFLD PiMZ was associated with more severe liver disease and need for liver transplantation. Suggests that if you have some other cause for liver disease, PiMZ will do less well.

J Pediatr Gastroenterol Nutr. 2006 Jul;43 Suppl 1:S30-5. [pmid:16819398]

About 10% of children with Z phenotype have prolonged (obstructive) jaundice as babies, most have abnormal LFTs at some point in first year of life. Only 2% progress to liver failure requiring transplantation, however. Risk of hepatocellular carcinoma higher, not surprisingly.

Augmentation therapy with IV AAT approved by FDA, expensive. May slow decline in lung function but not great evidence yet. No intended to treat liver disease.

Screening is really only useful in aggressive smoking and alcohol advice. Non-alcoholic fatty liver disease seems to worsen other causes of liver disease so avoidance of obesity seems important too.

Necrotizing panniculitis associated with AAT deficiency, seems to respond rapidly to AAT treatment.