Category Archives: Respiratory

Asthma and allergy stereotypes

Le Chiffre in Casino Royale may use a custom metal inhaler, but the implication is clear – he is not as masculine as James Bond.

“Mikey from “The Goonies,” who is portrayed as vulnerable and nervous and is seen taking puffs from his inhaler whenever a situation is particularly scary. Stevie from “Malcolm in the Middle” who suffers from severe asthma can barely make it through a sentence without gasping for breath and wheezing uncontrollably.

“Though he is also proclaimed a genius, it is this perceived weakness that becomes his defining characteristic.

“The stereotype even translates to cartoons, with Carl Wheezer from “Jimmy Neutron: Boy Genius” and Millhouse from “The Simpsons” represented as weak and timid individuals who are used as comic relief whenever they are upset and need a puff from an inhaler to control their symptoms triggered by anxiety.” [American lung association blog]

In the film Hitch, the lovable accountant Alfred uses his inhaler when he is scared to take action.  Until he is inspired to greater manliness, and he throws it away and mounts the steps to kiss his girl in passion, no longer shackled by his psychological, rather than medical, condition. [https://mbtimetraveler.com/tag/asthma-portrayal-in-television-and-movies/]

Even JK Rowling is guilty – see her TV show “The casual vacancy”.

Stephen King’s It has a hypochondriac asthmatic character Eddie Kaspbrak – although at least there is a genuinely terrifying scene where he has an asthma attack and his inhaler has run out – but even this has been triggered by bullying, enforcing the “nerd” stereotype.

Wheezy in Toy Story 2 is also a rather pathetic character.

Positive role models lacking. David Beckham and Harry Styles are some of the few.

Children with asthma, not surprisingly, are highly sceptical of such portrayals. Non asthmatic children obviously don’t appraise movie scenes for their meanings but they do judge the social context of the drama [https://pubmed.ncbi.nlm.nih.gov/22574393/]

Few if any other medical conditions seem to get the same treatment…

Asthma and Obesity

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?). 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.

Hay fever

=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 that children with hay fever requiring anti-histamines are significantly more likely (43%) not to achieve predicted exam grades, especially when using first generation sedating antihistamines such as Piriton (chlorphenamine)  [Samantha Walker, JACI 2007: 120; 381-387].

Associated with other atopic conditions, such as food allergy and asthma. 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 pract 2015]

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!  Average start of grass season in Scotland is the 1st of June (blue on chart below), peak is mid-June to mid-July.

Pollen seasons in Scotland – University of Worcester Pollen Lab

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)]

Management

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?

Air purifiers with a HEPA filter should help but doors and windows will need to be closed. Unfortunately the best ones tend to be big, expensive and noisy, and price does not mean good quality. Plus you have to remember to replace the filters. The cheapest Which? recommended one (the Electriq EAP500HC) costs over £200.

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.

Medicines

Antihistamines – oral, nasal or eye drops. Various, some people find one works better than another Sedating antihistamines eg Chlorphenamine should be avoided except at night.

Cromoglycate eye drops are available, they work in a different way from antihistamines so may give additional benefit. But need to be given 4 times daily, which is inconvenient.

Nasal steroids useful if used correctly. Fluticasone is licensed from age 4 – Betnesol nasal drops from age 2 (but systemic absorption an issue). Combination steroid/antihistamine spray available from age 12.

Leukotriene receptor antagonist licensed for hay fever in children with asthma.

Short courses of oral steroids might be justified for special occasions.

Immunotherapy available, grass (Grazax, Pollinex Grass and rye) or tree pollen (Pollinex tree) – metanalysis by Dhami S et al of grass desensitization in children, using either subcutaneous or sublingual therapy, found overall standardized mean difference (SMD) of -0.53 (95% CI -0.63, -0.42) in symptoms scores (roughly equal numbers of SCIT and SLIT studies, roughly equivalent scores)  [Allergy 2017]. Deaths reported in asthmatics with poor control.

Sublingual vs subcutaneous- 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.

Chest X-ray

Interpretation

  • Start outside, work in – soft tissues, then bones, then lungs/heart, finally neck/infradiaphragmatic.
  • Safety check – position of lines/tunes, check apices for pneumothorax, any foreign bodies?

Adequacy

  • Rotation – look at symmetry of clavicles and anterior rib ends.
  • If clavicles high, then lordotic film. May obscure apices.
  • Penetration – should just be able to make out intravertebral spaces, without lung fields being too dark.
  • Inspiration – hila become artificially prominent if underinflated.

Thymus

Pesky thing! Can look like pneumonia. Latter more likely if air bronchograms, volume loss (displaced fissure/trachea/mediastinum), effusion. Classically:

  • indentations where ribs overlie.
  • Pointy outside edge (“sail sign”).
  • No mass effect
  • Lowish density – should still be able to see vascular markings of lung behind

Spinnaker sign is where pneumomediastinum around thymus creates long curving line.

Other normal things

Azygos lobe – normal variant where RUL has near vertical line extending up and out, giving impression of mediastinal mass.

Mach effect – a line parallel to heart border, looks like pneumocardium but actually optical illusion where your eye “detects” border where there isn’t one…

One diaphragm usually higher than other – both ok, as long as no more than 2cm (one rib space).

Other

Hilum – rings or tram lines suggest bronchitis. Round opacity adjacent to and larger than ring suggests vascular prominence due to left to right shunt.

Silhouette sign – where heart border and/or diaphragm obscured in lower zone due to consolidation in lower lobe (left or right).

Effusion – vertical line at costophrenic angle.

Round pneumonia – will have air bronchograms, compare mass.

Collapse vs consolidation – sharp lower border is the fissure so if deviated then collapse.

Pneumothorax – lucency without clear edge may suggest lung hyperinflation eg bronchial atresia.

If edge projects below diaphragm then likely to be skin fold!

Foreign body – get expiratory film, which will enhance air trapping.

BTS/SIGN Asthma guidance

Latest revision 2019. See also asthma.

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.

Diagnostic algorithm for asthma

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 [colour code suggests this is appropriate from age 1, but no advice given for under 1…].

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
  • Vomiting
  • Wet/productive cough
  • Nasal polyps

Management

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.

Treatment

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

Levels of acute asthma attacks in children
  • 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:

  • PEF <33%
  • Exhaustion, poor resp effort [tautology?]
  • Hypotension
  • Cyanosis
  • Silent chest
  • Confusion

Treat –

  • Oxygen
  • 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].

Air pollution

According to the 2010 Global Disease Burden Assessment, outdoor air pollution caused more than three percent of the annual disability and life lost. Rising due to urbanisation. Responsible for 50 000 deaths annually in the UK.

Air pollution associated with low birth weight, smaller heads, developmental disorders eg autism, type 2 DM, strokes, heart attacks (atherosclerosis), cognitive decline, slower development of lung function with reduced adult capacity (implication for COPD), onset of asthma, wheeze. Not just exacerbations of chronic lung disease!

Different kinds of pollution – particulates (different sizes eg PM1), nitrogen dioxide, sulphur dioxide.  Most PM10 from traffic, but natural sources too eg pollen, soil.  Wood burners! NO2 and SO2 falling as fewer power stations and less industrial output, but NO2 particular problem for urban centres where most commercial vehicles run on diesel.

Diesel engines also produce polycyclic aromatic hydrocarbons eg BaP (Benzo pyrene), maternal exposure a concern as linked to mental health and neurodevelopmental problems in children. Some also carcinogenic.

Particulates a problem for respiratory conditions. Often contain spores and pollen. Ozone associated with airway hyperresponsiveness.

Not just about degree of pollution – metereological factors (temperature, atmospheric pressure, low humidity etc) complicate. In Taiwan, pollution synergistic with dust mites for development of asthma.

Carbon deposits found in fetal side placental macrophages. 

MRSA and stenotrophomonas colonization in CF associated with maternal PM levels.

European study of 325 000 adults found mortality increased proportionally with levels of particulate matter, nitrogen dioxide and black carbon – even at levels below current EU/US/WHO standards. [BMJ 2021;374]

Southern California reduced PM levels and found less severe chronic lung problems.

1 hour commuting in Sao Paolo estimated to be equivalent to  5 cigs/d.  In London, travel to school is bulk of exposure (plus school breaks! Note locations!) esp stationary traffic.

What cars produce in lab tests is not the same as in the real world, even when manufacturers don’t cheat!

Low emission zones generally exclude cars, and may just divert traffic elsewhere, not much evidence that they help. London low emission zone has reduced NO2 slightly only.  Plan for ultra low zone. 

[Abigail Campbell, SPRING meeting 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016370/ ]

SARS

Severe acute respiratory syndrome – caused by one of the coronavirus group, see also MERS and COVID19. The virus probably originated in bats, then crossed into humans via masked palm civets.

The virus spread beyond its original outbreak in China when a businessman became unwell on his flight out of China and died in Vietnam in 2003. Further outbreaks appeared rapidly, as far afield as Toronto. Eventually led to 8000 cases globally, but rapid surveillance and isolation measured brought the epidemic to an abrupt end within 4 months.

Super shedders exist, who have much higher infectivity (1 case on a plane infected 120 others, whereas another plane had 4 cases on board, but no secondary cases occurred!). On the other hand, there is no documented transmission by asymptomatic cases, or between children.

Incubation period is 5-7 but up to 14 days. Spread is by respiratory, fomites, and faecal-oral routes. Peak shedding occurs at peak of clinical disease hence outbreaks were often among health care workers.

Symptoms are ‘flu-like, and non-specific. Fever is universal. Those who do badly have sudden deterioration on 10th day, with ARDS. Mortality is around 10%, but very age dependent, reaching over 50% in the over 65s. Children have lower viral loads, and generally have a benign course. Compared with adults, they perhaps get more gastrointestinal symptoms than respiratory.

Children under 5 yrs are hardly affected at all – perhaps because recent coronavirus infection protective, perhaps because of reduced immune reactivity.

No long term morbidity seen in children.

The diagnosis is suggested by the paucity of clinical signs (mild crepitations only, if anything) with an abnormal chest radiograph (non-specific), and laboratory evidence of leucopenia, lymphopenia, and thrombocytopenia. Raised AST/ALT also seen.

Definitive diagnosis is by ELISA or PCR, neither of which is very sensitive, or useful early on in disease.

Interferon alpha appears to be of benefit in vitro. Otherwise supportive.

Personal Protective Equipment effective if used properly – so buddy system.

Infection control – encourage self isolation, dedicated staff etc.

MERS

Middle East respiratory syndrome, caused by a coronavirus
(MERS-CoV) . See also COVID19 and SARS.

Reported 2012.  More than 2000 cases so far, mostly related to Arabian peninsula, but a single case of MERS-CoV in a returning traveller led to an outbreak involving 186 cases across 16 hospitals in the Republic of Korea.

36% mortality, mostly people with co-morbidities. More than 2000 cases so far. 

One of WHO blueprint priority diseases – potential for serious outbreak, no treatment or vaccine (6-7 others: SARS, Crimean-Congo HF, Ebola, Lassa etc).

Incubation time 2-5 days but up to 14. Median onset to hospitalisation 4 days.

Risk factor appears to be camel contact – milk, meat, urine.

Management

Management based on experience of SARS etc.

Infection control – negative pressure, dedicated staff, cleaning, PPE for suspected cases, self isolation for close contacts. 

COVID19

Hogmanay 2019 WHO were informed of cluster of cases of Pneumonia of unknown cause in Wuhan city, Hubei province, China.

Novel coronavirus identified, named SARS-CoV-2. COVID19 is associated disease. Distinct from coronaviruses responsible for SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) but of course these are both similarly capable of causing severe disease, whereas many coronaviruses pretty benign.

By end of February 2020, more than 70 000 cases reported across China, 2500 fatalities. Pandemic was declared by WHO on 11th March.

Cruise ships including the Diamond Princess in Japan (over 700 cases) and the Zaandaam were particularly hard hit.

Lockdown declared in UK on 23rd March.

Binds to ACE2 – potentially explaining particular susceptibility among people with hypertension and Africans (nearly double rate of whites) and Asians (although Indian rates lower than Bangladeshi/Pakistani). Rates among Chinese females actually lower than among Whites! [UK data]

At least 3% of severely affected people have known or previously unrecognised genetic defects in type 1 interferon production (especially TLR3 and IRF7 which amplify production).

Risk of “critical illness “ from COVID-19 RR 1.44 if overweight, 1.97 if obese. UK OpenSAFELY analysis. Death 1.27 if BMI 30-39, 2.27 if BMI>40. ACE-2 higher in obese. Plus different immune responses and challenges to ventilate.

London has double the age standardised mortality of any other part of the UK (Birmingham next), as high as 144 per 100 000 in Newham. Glasgow’s rate is about 80 [UK data].

Diabetes, cancer and poorly controlled asthma associated with death in primary care records study. Residential care homes, health care workers, social deprivation, Black/Asian groups also seem to be particularly at risk of death.

Bronx worse hit than Manhattan, despite similar population density. Higher attack and death rates among Afro-Americans. Role for air pollution too?

Plot of mortality rates by gender/race

Pregnancy increases risk slightly, not much risk to baby although elective preterm delivery may be part of management of sick mother.

Acute neurological presentations in adults, including stroke and Guillain Barre syndrome.

Transmission from asymptomatic cases seems to be less important than symptomatic and pre-symptomatic (1-2 days).

See Treatment.

COVID in Children

Probably more severe than SARS but still children tend to be less severely affected than adults. Cross protection from immunity from other coronaviruses? Differences in ACE2? Some asymptomatic.

16% of hospitalised children admitted to critical care. Age under 1 yr, or age 10-14 yrs, co-morbidities, black ethnicity are risk factors for critical care admission. Mortality rate less than 1% in hospitalised [Swann, ISARIC study]. 3 PIMS deaths in England, all 10-14yrs. 70% of all COVID related deaths in non-white groups. 24% of deaths had no co-morbidities, 60% had life limiting condition. No deaths in kids with asthma, diabetes, Trisomy 21.

Wheeze uncommon.

X-ray more often negative; CT more sensitive.

Can present with GI symptoms.

One baby born to an infected mother developed severe complications.

Neutrophil and LDH counts go up, lymphocytes go down.

A small series of children with COVID-19 has shown a greater prevalence of peripheral halo (halo-sign) lung consolidations on CT.

The criteria for the definition of Acute Respiratory Distress Syndrome (ARDS) and septic shock, the guidelines for the management of sepsis and septic shock and the use of non-invasive ventilation in children are different from those of adults.

Children desaturate more easily during intubation; therefore, it is important to pre-oxygenate with 100% O2 with a mask with a reservoir before intubating.

A rectal swab may be useful in children to determine the timing of the termination of quarantine.

[Chengdu and Italian experience, from PIPSQC]

WHO supports use of dexamethasone in patients with acute respiratory presentation and hypoxia (sats<90%), tachypnoea, or severe respiratory distress. RECOVERY trial continues to study dexamethasone in neonates, plus roles for azithromycin and toculizimab.

Sotrovimab is first line treatment, Remdesivir second line is licensed in hospitalised patients in oxygen, over 12 years and over 40kg and can be considered in this age group for patients with high-risk comorbidity for non-hospitalised patients also. Treatment should be commenced within 5 days of symptom onset (Sotrovimab), within 7 days of symptom onset (remdesivir). Paxlovid (Nirmatrelvir plus Ritonavir) is alternative first line option in adults.

Paediatric multi inflammatory syndrome associated with COVID19 (PIMS-TS)

See PIMS.

Cystic Fibrosis

The most common inherited genetic condition in N European populations, with carrier rate of 1 in 20. Incidence is therefore around 1 in 4000 births. Most common gene defect is deletion at delta F508 of CFTR (CF transmembrane conductance regulator) gene.

Features:

  • family history
  • congenital intestinal atresia
  • meconium ileus
  • distal intestinal obstruction syndrome
  • faltering growth (in infants and young children)
  • undernutrition
  • recurrent and chronic pulmonary disease, such as:
    • recurrent lower respiratory tract infections
    • clinical or radiological evidence of lung disease (in particular bronchiectasis)
    • persistent chest X-ray changes
    • chronic wet or productive cough
  • chronic sinus disease
  • obstructive azoospermia (in young people and adults)
  • acute or chronic pancreatitis
  • malabsorption
  • rectal prolapse (in children)
  • pseudo-Bartter syndrome.

Median predicted life expectancy is now nearly 50 years, but this doesn’t take into account the new CFTR modulators. Management has evolved slowly, with revolutionary improvements including high calorie diets/feeding, pancreatic enzyme replacement, specialist CF centres and CF newborn screening.

Drugs

  • Regular prophylactic antibiotics (usually starting with oral flucloxacillin) introduced at early stage. Later on may require regular courses of IV antibiotics.
  • Azithromycin given on Mondays, Wednesdays and Fridays – but for anti-inflammatory properties as much as antibacterial.
  • Creon is the name for pancreatic enzyme supplements, taken with each meal.
  • Fat soluble vitamins.
  • Nebulised DNAse and hypertonic saline to help with chest physiotherapy

New treatments

CFTR modulators treat the basic defect. Lead to significantly improved pulmonary function, decreased respiratory infections and improved nutrition.

Combination elexacaftor, tezacaftor and ivacaftor, will be suitable for approximately 90% of all people with CF. But expensive, with many countries unwilling or unable to fund them.

CFTR phenotypes vary. Class I–III variants are most severe, with minimal or no CFTR function. Class IV–VI variants are where CFTR is produced and reaches apical membrane but doesn’t work normally, so milder phenotype.

Ivacaftor reduces hospital admission, rates of respiratory Pseudomonas and Aspergillus infection, and halves rate of decline in FEV1 %, suggesting at least 5 years survival benefit.

[http://dx.doi.org/10.1136/archdischild-2020-320680]