Table 15.1 gives an approach to the cardiorespiratory examination (specifically) of the NICU graduate. It does not include looking for other complications of prematurity (e.g. IVH), but does include toxicities relating to ventilation and oxygen.

Table 15.1 An approach to the cardiorespiratory examination of the NICU graduate

General observations

Parameters

• Weight

• Height

• Head circumference

• Percentiles

Sick or well, pallor, cyanosis, alertness, movement Nutritional status: visual scan for muscle bulk, fat Respiratory

• Distress (tachypnoea, tracheal tug, intercostal, subcostal recession)

• Audible wheeze

• Stridor (subglottic stenosis, vocal cord damage from intubation)

• Cough

• Cyanosis

• Oxygen cannula

Chest Inspection Breathing pattern Respiratory rate Chest deformity

• Pectus carinatum

• Increased anteroposterior diameter (hyperinflation)

• Rib rosary (vitamin D deficiency)

Scars

• Previous tracheostomy

• Intercostal catheters

• Repair of patent ductus

Palpation: •Tracheal position •Apex position •Palpable pulmonary valve closure •Right-ventricular overactivity Percussion can be deferred until after auscultation, as it may cause crying in younger infants Auscultation Lungs

Heart

• Loudness of second heart sound (pulmonary hypertension)

• Murmur of PDA

Percussion For hyperinflation, consolidation After the above, palpate the liver for ptosis (hyperinflation) and percuss for liver span (hepatomegaly from congestive cardiac failure [CCF]) Upper limbs Hands: scars of previous intravenous cannulae Nails

Pulse

• Pulsus alternans (CCF)

Blood pressure: hypertension (renovascular hypertension due to umbilical catheter, corticosteroid use or renal dysfunction) Head Eyes

• Nystagmus (ROP)

• Visual acuity (ROP)

• Fundi: ROP (and grading of this)

Nose: deformity due to prolonged intubation Lower limbs Palpate for ankle oedema (CCF) Other Temperature chart (infection)

CCF = congestive cardiac failure; PDA = patent ductus arteriosus; ROP = retinopathy of prematurity.

Management

Adequate oxygenation (and nutrition discussed below) is the most important factor for growth and development. Home oxygen is usually administered via nasal prongs. Low-flow oxygen (less than 2 litres/min) can be provided via various different-sized cylinders. All families must be supplied with cylinders: size E, which are small and portable, and size C, which are larger and to be kept at home.

Oxygen is needed if the child’s PO₂ in air is below 60 torrs. The aim is for the oxygen saturation (SaO₂) to be between 94% and 98% in the awake and asleep phases. Aiming for higher levels may worsen lung disease, and does not necessarily improve long-term growth or development. The actual range is controversial. Neonatologists generally use a lower limit of 90%, but respiratory physicians generally use a higher range (>94%), which is probably reflective of the age of infants and hence the risk of ROP. In the early phase, a lower SaO₂ is usually accepted, but upon discharge when infants are well over the corrected term of gestation, a higher minimal SaO₂ is usually used. Oxygen administration is associated with increased weight gain, decreased pulmonary hypertension, decreased SIDS-like events, and decreased morbidity and mortality. Home oxygen therapy avoids prolonged and expensive hospitalisation.

At discharge from NICU, the average requirement for CLD is low-flow subnasal oxygen at 250–1000 mL/min. The median duration of oxygen requirement is 6–10 months. Weaning should occur very slowly, over about 12 weeks, guided by regular saturation monitoring. An intercurrent acute respiratory tract infection may require reinstitution of oxygen.

Increased oxygen is needed during increased activity, feeding and sleeping (rapid eye movement sleep is associated with increased activity and irregular breathing, and carries a risk of hypoxia), so that monitoring of these times indicates when the child is able to cope in air. Oxygen is discontinued first when awake, then eventually when asleep. These children may be admitted to hospital overnight, for oximetry off oxygen while asleep. If the saturation level is consistently below 94%, oxygen therapy is still required; if it stays at or above 97%, then oxygen can probably be discontinued. Alternatively, as an outpatient, a period of oximetry for one hour when awake demonstrating saturations consistently above 97% indicates that supplemental oxygen is no longer required. Once oxygen is discontinued, weight gain is watched closely over the ensuing few weeks to ensure that adequate growth is occurring. As above, note variation of acceptability of minimum SaO₂.

Growth and development

Children with CLD are at high risk of associated neurodevelopmental and growth problems. Much of the child’s energy expenditure is related to the work of breathing, and this contributes to failure to thrive unless nutritional supplementation to 120–150% of usual requirements is achieved. Motor delay is not uncommon (e.g. poor muscle bulk, general debility) and, if not associated with intellectual impairment, may improve with time. Developmental assessment (intellect, vision, hearing) is regularly performed to enable appropriate intervention.

Nutrition

As mentioned above, adequate nutrition is of paramount importance. Tachypnoeic infants do not feed well, the time they take for a breastfeed or bottle being proportional to the severity of their CLD. As these children may need to avoid fluid overload, the quality of feed should be altered, not the quantity. Usual requirements are around 140–180 kilocalories (kcal) per kilogram per day, but the real test is whether the child grows, and these figures are guides only. Calorie supplementation may be achieved by increasing the caloric content of infant milk formulae to 24–32 kcal per 30 mL. Added calories may comprise increased measures of milk powder (extra scoops), glucose polymers, vegetable oil or medium-chain triglyceride oil. In breastfed infants, small-volume high-calorie supplements can be given. Calorie wastage must be avoided; this occurs when too many calories are given.

Reasons for ‘difficult feeding’ include oral aversion, volume or acid reflux, aspiration (especially when neurodevelopmental problems are present) and dysphagia. Another problem is the lack of oral intake early (while in NICU), with poor tolerance to and lack of interest in feeds, which may persist. Some children require feeding at night via gastrostomy (often with fundoplication), particularly infants with gastro-oesophageal reflux. Nasogastric tube feeding is generally avoided (it can aggravate reflux and cause increased nasal problems), but is sometimes necessary. Provision of adequate vitamins and minerals (especially iron, folate and fluoride) is important. Supplemental oxygen can improve nutrition.

Obstructive airways disease and bronchodilators

These patients have obstructive lung disease, but variable airway hyperactivity, and lack uniformity in their response to drugs. Many have hypertrophied lung smooth muscle and respond to bronchodilators (even when preterm) earlier than true ‘asthmatics’. Combinations of inhaled beta-2 agonists, ipratropium bromide and inhaled corticosteroids are widely used, with variable success. Most units try these medications for at least some weeks to ascertain efficacy. Despite the common usage, there is inadequate long-term data to recommend the use of any beta agonist, or ipratropium bromide, in CLD.

Fluid balance and diuretics

These infants tend to accumulate interstitial lung fluid; fluid overload should be avoided. Fluid intake of up to 180 mL/kg per day are usually well tolerated. Diuretics may need to be used (especially in children with some degree of cor pulmonale). Diuretics may act as pulmonary vasodilators. Initially, frusemide with potassium supplementation is used for short periods. For longer-term use, hydrochlorothiazide and spironolactone may be used (fewer side effects than frusemide). Serum urea and electrolytes should be monitored to avoid side effects (hypokalaemia, hyponatraemia, metabolic alkalosis). Prolonged frusemide therapy (over 2 weeks) can cause renal calcification, detectable on ultrasound. Diuretics improve lung mechanics and oxygenation in the short term only; no long-term benefits have been demonstrated.

Immunisation and RSV immune prophylaxis

Routine immunisation is particularly important in these children. Often allowed to lag behind because of their prolonged stay in the NICU, immunisation should be given at the appropriate chronological age, uncorrected for prematurity. Some units use RSV Ig. Prophylaxis with IV or IM RSV Ig (which is very expensive) significantly decreases the incidence of RSV infection and subsequent hospitalisation by about 50%. It can be given on an individual needs basis on discharge from hospital, and then monthly during the peak RSV season. The other preparation used for immune prophylaxis is palivizumab, a humanised RSV monoclonal antibody given intramuscularly. Infants with a gestational age below 28 weeks can benefit from prophylaxis up to 12 months of age, whereas infants with a gestational age of 29–32 weeks may benefit up to 6 months of age. Treatment is for children under 2 years of age who are still having oxygen, and is used in the anticipated RSV season for 4–6 months of the year.

Avoidance of tobacco smoke

Smoking in the house is forbidden if a baby is receiving oxygen, because of the fire hazard. However, exposure to smoke still occurs. Exposure to smoking increases pulmonary inflammation, worsens lung function, increases the risk of developing respiratory tract infections and increases the risk of cot death. Parents should be encouraged to stop smoking, but this is rarely successful, and this is a difficult issue. At the very least, parents should be encouraged to smoke outside of the house, well away from any verandah/patio or front or back doors, wearing some sort of jacket or shirt, and a hat, to decrease the deposition of tobacco smoke on the parents’ own clothes, hair and skin, and then take off the hat and jacket, leaving them on a hook outside the house, and then wash their hands and face (and ideally clean their teeth) before going near the child.

Social issues

The degree of psychosocial difficulty depends to some extent on the associated problems that the child has. If there is severe neurological impairment, there is a parental separation rate approaching 50%. There tend to be three phases after the initial discharge of the child from hospital: first, a ‘euphoric’ phase, which may last about 6 weeks; then a period of despair and exhaustion, lasting from around 6 weeks to 6 months post-discharge; and finally the stage of acceptance. Another common problem is the ‘vulnerable child syndrome’, a parent–infant behaviour disorder that may include problems with feeding, difficulty separating from the mother, overindulgence and overprotection, leading to the child ‘running the household’. This may be prevented by spending more time with the parents, educating them in potential problem areas that are well recognised, by normalising the management of the baby, and by normal and appropriate discipline.

Associated apnoea and bradycardia

Children with CLD appear to be at higher risk of apnoea and sudden death than other infants. Some units provide monitors for the first few months after discharge home. Sleep laboratory studies may show unrecognised bradycardia/apnoea and may guide therapy (e.g. caffeine), but are not useful in prognosis. Adequate oxygenation by low-flow oxygen is the most important aspect to prevent unrecognised hypoxia and bradycardia.

Prognosis

Most problems with CLD occur in the first year of life. Long term, most children with CLD have minimal functional abnormalities, mainly due to the increase in the number of alveoli that occurs from birth (20 million saccules at term; air/tissue interface 2.8 m²), producing new alveoli up to 8 years old (300 million alveoli; air/tissue interface 32 m²).

Cystic fibrosis (CF)

This is a common long case and it is expected to be handled well. CF is becoming an adult disease with, currently, some 45% of CF patients in Australia being adults. Survival continues to increase, with overall mean survival in Australia at the time of writing (2010) at around 40 years (males older, females younger). This improved survival is the result of standard care, intervening earlier and aggressively treating every respiratory exacerbation, optimised by the ability to eradicate Pseudomonas (in 1998, 44% colonised with Pseudomonas, versus 12% in 2007), the optimal use of mucolytics (pulmozyme, hypertonic saline 6%), utilising the anti-inflammatory effects of azithromycin, and recognition of the utility of segregation clinics (Pseudomonas and non-Pseudomonas, MRSA and non-MRSA, cepacia and non-cepacia). Increasingly, CF is recognised as an ‘antibiotic deficiency disease’; BAL studies have shown a veritable bacterial pathogen soup, in airways of patients as young as 3 months: Staphylococcus aureus (comes early and stays); Pseudomonas aeruginosa (comes early and stays); Haemophilus influenzae (declines in later year); E. coli, Streptococcus pneumoniae, Klebsiella species and Enterobacter. Discussion in the long case could well centre around aspects other than lung disease, as longer survival has led to more patients developing complications such as cystic fibrosis related diabetes (CFRD) and musculoskeletal disorders.

Genetics

Cystic fibrosis is autosomal recessive. Molecular genetics: cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR); the locus is on the long arm of chromosome 7 (7q31.2), and the protein is called CFTR. Over 1525 different mutations in the CFTR gene are known; almost all are point mutations or small (1–84 base pair) deletions. The CFTR gene codes for a 1480-amino-acid integral membrane protein of 170 kDa, a cyclic-AMP-regulated chloride channel on the apical surface of epithelial cells. The deficiency of CFTR function leads to abnormal regulation of chloride channels and decides the phenotype of the epithelial cells. The most common mutation worldwide is delta-F508, where there is deletion of phenylalanine at the 508th amino acid within the CFTR protein; this accounts for 30–80% of mutant alleles, depending on the ethnic group.

There are five functional classes of mutation in CF:

• Class I mutations cause reduced or absent synthesis of CFTR, and are associated with nonsense, frameshift or splice junction mutations (e.g. G542X: 2.5% of cases; no synthesis of CFTR).

• Class II mutations cause a block in protein processing, and are associated with missense mutations and amino-acid deletions (e.g. delta-F508: 70% of cases in Australia; blocked processing of CFTR).

• Class III mutations cause a block in the regulation of the CFTR chloride channel, and are associated with missense mutations (e.g. G551D: 1.6% of cases; blocked regulation of CFTR).

• Class IV mutations cause altered conductance of CFTR chloride channel, and are associated with missense mutations (e.g. R117H: 0.3% of cases).

• Class V mutations cause decreased splicing of normal CFTR, which decreases membrane CFTR function and can act concurrently with other mutations on the same allele.

Different mutations are more common in different countries. It is not necessary to be homozygous for the same mutation to have CF. The most common defects can be detected within hours by polymerase chain reaction (PCR). Gene mutations are weakly correlated with clinical severity: genotype/phenotype correlations are strongest for pancreatic insufficiency, with patients homozygous for the delta-F508 mutation being almost always pancreatic insufficient (99%). Classes I–III mutations tend to produce more severe disease than IV–V mutations. The gene frequency in most Caucasian populations is 1 in 25, giving an incidence of 1 in 2500. In contrast, incidence in African-Americans is 1 in 15,000 and in Asian populations approximates 1 in 31,000.

History

Presenting complaint

Reason for current admission: often a combination of loss of weight, appetite and energy, and an increase in cough, sputum and school/work missed, warranting a ‘tune up’. This is timed to fit in with the family; for example, before holidays.

Current status

Respiratory disease

1. Symptoms: upper respiratory tract infection (URTI) symptoms, impaired exercise tolerance (important but relatively uncommon in children); cough frequency, severity (cough syncope extremely rare), nocturnal or exercise-induced wheeze or asthma, recent change in pattern; sputum volume, colour, blood and any recent change in these; fatigue, dyspnoea, wheeze, response to bronchodilators, peak flow pattern (limited value); need for home oxygen; chest pain; chronic sinusitis; glue ears; nasal polyps (nasal polyps produce symptoms of rhinorrhea, nasal blockage, snoring and even occasionally have protruded from the nose).

2. Infective agents: acquisition of chronic infection with Pseudomonas is an important prognostic factor, with early acquisition (under 5–6 years) of mucoid Pseudomonas being associated with increased mortality, especially in females, and increased morbidity. Also Burkholderia cepacia acquisition is important.

3. Past complications; for example, pneumothorax, moderate-to-large haemoptyses, allergic bronchopulmonary aspergillosis (ABPA).

4. Investigations; for example, sputum colonisation, chest X-ray, pulmonary function tests, overnight oximetry.

5. Home management; for example, exercise, physiotherapy (frequency, type and by whom), PEP mask; nebulised antibiotics, saline, bronchodilators, or dornase alpha; pMDIs (bronchodilators, ICS); oral antibiotic or corticosteroid; venous port access for parenteral antibiotics.

6. Future therapy plans: use of newer antibiotics, oral or nebulised; corticosteroids; consideration of lung transplant, gene therapy, experimental therapies.

Gastrointestinal disease

1. Symptoms; for example, growth, weight loss, appetite, dietary history, stool pattern (oily, pale, bulky or offensive, blood, melaena), passing wind and burping (may not be popular, but can have an impact on kids at school), abdominal pain, vomiting, haematemesis, heartburn.

2. Past complications; for example, meconium ileus or equivalent (this is now termed DIOS [distal intestinal obstruction syndrome]), rectal prolapse, jaundice, portal hypertension, fibrosing colonopathy, gastrostomy.

3. Investigations; for example, faecal fat studies, liver function tests, hepatobiliary ultrasonography or Tc-99m scintigraphy.

4. Home management; for example, pancreatic enzymes, vitamins, salt tablets.

5. Future plans; for example, gastrostomy, sclerotherapy, liver transplantation.

Other systems

Symptoms, past complications including episodes of dehydration (which is a significant problem in warmer climates, and which increases the risk of pneumonia and DIOS), investigations, home management and future plans regarding diabetes mellitus, cardiac disease, growth failure, pubertal delay and arthropathy.

Past history of CF

Initial symptoms, investigations and management prior to diagnosis, diagnosis (when, where, how), subsequent investigations and management, progress of the disease, hospitalisation details (frequency, duration, usual treatment), complications of the disease and treatment, outpatient clinics attended (where, how often, routine tests performed), any recent change in symptoms or management.

Immunisations (especially pneumococcal, influenza vaccines).

Venous access is a serious issue, especially as aggressive treatment now starts earlier. The complications of totally implantable venous access devices can be serious.

Allergy may be an important issue, with some children requiring desensitisation.

Social history

Disease impact on patient

Treatment regime, disruption of going to hospital, recurrent/permanent loss of: normal social life, being part of peer group, being part of family, freedom, independence, normal childhood, trust, self-esteem (impaired growth, development, may have short stature, delayed puberty, gastrostomy button, intravenous access ports, offensive flatus, cough, requirement for treatment [pancreatic enzymes, vitamins, bronchodilators], decreased ability for physical activity, stamina). By around 8–12 years, aware of differences from normal peer group, and shame and embarrassment can become very prominent. There is the question of ‘Why me?’ Other issues: seeing friends or relatives with CF deteriorating in hospital, requests for transfer to adult care, compliance (reluctant to take medications in front of peers), schooling (attendance, performance, teacher awareness of disease and its treatment, peer interactions), employment prospects, limitation of activities of daily living (including sport), depression (inevitability of death), consideration of marriage, and prevention (smoking). Fertility must be discussed: What has been said and to whom? Many units normally talk with boys around 14 years of age and discuss all health-related issues, including normal sexual function, reduced ejaculate, and choices for the future with micro-aspiration sperm and IVF techniques. Smoking must be discussed. Alcohol is another discussion area for the pancreatic-sufficient children, as they have an increased risk of pancreatitis.

Disease impact on parents

Restricted social life, marriage stability, maternal depression, denial, fears for the future, requirement to stop smoking, financial considerations (medical treatment, food, travel, petrol, parking fees, awareness of benefits available, modifications of holiday plans), problematic parenting (overprotective or too lenient), knowledge of terminal nature of CF, time constraints of treatment regime, most treatment is organised/carried out by the mother.

Disease impact on siblings

Sibling rivalry, hostility, isolation, alienation, resentment, guilt (‘survivor guilt’), concern, worry, effect of family’s financial burden, genetic counselling. There are camps for siblings (e.g. CFQ sibling camps). A useful website is www.siblingsaustralia.org.au.

Disease impact on family unit

Factors that impact on family adaptation include the severity of the disease, the illness course, the financial costs, the stability of the family and their support network. Frequent coping styles include optimism, relying on self, humour, realistic appraisal of circumstances and maintaining normal lifestyle.

Social supports

Social worker (their role: advocacy, liaison with school, organising referrals, evaluating child protection risks), Cystic Fibrosis Association, community nurse, extended family, close friends, CF ‘social network’, respite from managing child, financial support.

Coping

Who attends with the patient, who gives treatment, confidence with management, parents’ main concerns, degree of understanding of the disease, expectations for the future, understanding of prognosis (by patient and parent).

Access

To local doctor, paediatrician, cystic fibrosis clinic sister, Cystic Fibrosis Association, hospital.

Family history and genetic aspects

Other members with CF; whether other siblings screened, more children planned, prenatal diagnosis (and subsequent management for positive result) discussed; patient’s fertility, female patient’s contraception, pregnancy risk (have these been addressed?).

Immunisation

Routine, early measles immunisation, gammaglobulin for measles contacts, requesting yearly influenza vaccine.

Examination

The approach given in Table 15.2 assesses patients with CF for disease progression, severity and the current status of the disease. It looks particularly at clubbing, flap, chest deformity, cor pulmonale, nutrition, puberty, diabetes, chronic liver disease and hypertrophic pulmonary osteoarthropathy. Two very important signs are the cough and the sputum, and these may give a better indication of the state of the lungs than any other finding on physical examination.

Table 15.2 Examination of the child with cystic fibrosis

General inspection

Position patient: standing, with adequate exposure, for a complete examination, but sensitive to the patient’s modesty—although ideal, the patient being fully undressed (as stated in previous editions) is neither practical nor sensitive in most patients, and should not be encouraged

Parameters

Sick or well Pubertal status (delay) Vital signs

• Respiration

• Pulse

• Temperature

• Urinalysis (glucose)

Nutrition

• Muscle bulk (protein); e.g. biceps, quadriceps

• Subcutaneous fat, e.g. mid-arm, subscapular

• Pallor (anaemia)

Peripheral stigmata of CLD Oedema (hypoproteinaemia) Upper limbs Nails

• Clubbing

• Cyanosis

• Leukonychia (CLD)

Fingers

• Fingertip prick marks (BSL testing)

• HPOA

Palms

• Erythema (CLD)

• Crease pallor (anaemia)

Pulse

• Paradoxus (severity of airway obstruction)

• Alternans (CCF)

• Bounding (hypercarbia)

Flap

• Hypercarbia

• Liver failure (rare)

Joints: arthropathy Skin

• Bruising or petechiae (CLD, vitamin K deficiency)

• Spider naevi (CLD)

• Scratch marks (cholestasis)

Muscle: bulk (palpate, if not done already) Axilla: hair, odour (Tanner staging) Head Eyes

• Conjunctival pallor

• Scleral icterus

• Retinal venous dilation (hypercarbia)

Ears

• Secretory otitis media

• Hearing (aminoglycosides)

Nose: nasal polyps Mouth

• Angular cheilosis

• Central cyanosis (lips, tongue)

• State of teeth, dental hygiene

• Oral thrush

Face

• Cushingoid (systemic corticosteroids)

• Acne and facial hair (pubertal status)

Chest Inspection

• Chest deformity: pectus carinatum, increased AP diameter (hyperinflation), thoracic kyphosis

• Scars: previous pneumothorax, bilateral lung transplant, venous access port (e.g. Port-A-Cath, Hickman)

• Tanner stage of breast development

• Harrison’s sulcus

• Chest expansion

Cough: moist, productive, request sputum Perform peak flow measurement if meter available (limited usefulness) Palpation: tracheal position, apex position, palpable pulmonary valve closure, right-ventricular overactivity Percussion for hyperinflation, consolidation Auscultation (note: may be normal even in moderately severe CF)

• Air entry

• Breath sounds

• Vocal resonance

• Adventitious sounds

• Crackles

• Wheezes

• Loudness of second heart sound (pulmonary hypertension)

• Gallop rhythm (cor pulmonale)

Abdomen Inspection

• Distension (poor abdominal musculature with protein–calorie malnutrition, ascites with CLD)

• Scars (e.g. gastrostomy, previous meconium ileus, hepatobiliary surgery for common bile duct stenosis, fundoplication)

• Venous access port (e.g. Infuse-A-Port)

• Prominent abdominal wall veins (CLD)

• Needle marks (diabetes mellitus)

• Tanner stage of pubic hair

• Striae (corticosteroids)

Palpation

• Liver ptosed (chest hyperinflation); liver edge—is it firm, or is it bumpy (cirrhotic)?

• Hepatomegaly (fatty liver with malabsorption or corticosteroid use, CCF with cor pulmonale)

• Splenomegaly (portal hypertension)

• Faecal masses (DIOS can present as a right iliac fossa mass)

• Herniae

Assess for ascites (fluid thrill, shifting dullness) Examine genitalia

• Tanner staging

• Hydrocoele

Inspect anus for rectal prolapse Lower limbs Inspection

• Toe clubbing

• Bruising (vitamin K deficiency, CLD)

• Joint swelling (arthropathy)

Palpation: ankle oedema (hypoproteinaemia) Gait examination

• Peripheral neuropathy (vitamin E deficiency)

• Cerebellar ataxia (vitamin E deficiency)

• Proximal muscle weakness (corticosteroids)

(Note that clinically evident vitamin deficiencies are very rare in CF, so signs of vitamin A and D deficiencies are extremely unlikely to be seen)

BSL = blood sugar level; CCF = congestive cardiac failure; CLD = chronic liver disease; HPOA = hypertrophic pulmonary osteoarthropathy.

Investigations

Diagnostic

Neonatal screening

Most infants with CF are detected in this way in Australia at present (2010), as neonatal screening is now universal across Australia and New Zealand. Each Australian state performs this slightly differently, although all check immunoreactive trypsin (IRT) on the neonatal screening blood test, followed by gene analysis on the top 1% IRTs. Blood immunoreactive trypsin (IRT) levels are measured in the Guthrie blood sample. IRT levels in CF are 2.5–7.5 times the normal range. Samples with IRT levels above the 99th centile are tested for the delta-F508 mutation. Homozygotes are detected directly. Heterozygotes are recalled for sweat testing. Making the diagnosis when children are presymptomatic does have a significant positive impact on prognosis.

The critical aspect is accurate diagnosis; it needs to be confirmed. Sweat tests should be carried out only in centres that do at least 50 per year (so private pathology laboratories may not be appropriate places to do this test). The diagnosis is made based on two mutations plus a positive sweat test, or consistent clinical features, or one mutation plus a positive sweat test. It is possible to have two mutations, but a normal sweat test and no clinical manifestations (except probably male infertility). Also, there can be difficult scenarios with borderline sweat test results. Two mutations alone does not equal diagnosis; these children are at risk of CF-related disease over time.

Sweat testing

The Gibson–Cooke classic technique requires 100 mg of forearm sweat obtained by pilocarpine electrophoresis. In 98% of CF patients, sweat chloride is >60 mmol/L, and this is diagnostic. However, 2% of patients have sweat chlorides below this level, usually between 50 and 60 mmol/L (the equivocal range), but about 1 in 1000 will have a value in the forties, and may require direct gene probing or pancreatic stimulation testing. False-negative results can occur in children with pancreatic sufficiency or oedema. False-positive results can occur in children with malnutrition (e.g. due to coeliac disease or emotional deprivation), immune deficiency (e.g. AIDS, hypogammaglobulinaemia), eczema, adrenal insufficiency and hypothyroidism.

Other

Pancreatic stimulation testing can diagnose CF in cases with normal or borderline sweat tests; it will always reveal abnormal ductal function in CF. At diagnosis, patients need a faecal sample to check for fat globules, chymotrypsin or elastase, to document the presence and severity, or absence, of steatorrhoea. Eighty-five per cent of CF patients have fat malabsorption (stool fat output over 7% oral fat intake); that is, they have pancreatic insufficiency (PI). Serum vitamin levels are checked early, as vitamin E deficiency can be corrected and may result in improved IQ (compared to loss of IQ with persistent vitamin E deficiency).

Monitoring of disease

Not many routine tests are done in CF:

1. Routine clinic visits, usually at least every 3 months: note weight, nutrition, sputum, spirometry.

2. Documentation of disease progression at intervals of 6 months to 1 year. The following may be done: chest X-ray (CXR), pulmonary function tests, liver function tests, full blood count, measurement of skin fold thickness. Vitamin levels and work-up for ABPA with total IgE can be performed annually. A high-resolution CT scan of the thorax in primary and secondary school can assess progress of bronchiectasis.

Other investigations as indicated

1. Cardiac: electrocardiography, echocardiography (right-ventricular hypertrophy) usually only done when heading for transplant.

2. Gastrointestinal: serum protein and albumin, liver function tests, coagulation studies, abdominal X-ray (meconium ileus, equivalent or peritonitis), abdominal ultrasound (gallbladder, liver), hepatobiliary Tc-99m scintigraphy (common bile duct strictures), percutaneous transhepatic cholangiogram (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) to detect strictures, pancreatic function tests.

3. Other. Whether CFRD should be screened for, with an oral glucose tolerance test (GTT) in children over 10 years, is debatable. A fasting blood glucose is not particularly useful in this context, as it does not exclude diabetes and can be normal in patients with significant CFRD; a GTT is a better test. Urea and electrolytes may be used to assess salt loss, and dye studies in patients with venous access ports can be used for assessment of port function.

Management

The aims of management include: (a) ensuring optimal growth and development; (b) delaying the progress of pulmonary disease; (c) preventing/treating complications; (d) normal lifestyle; (e) patient and family education; (f) the recognition and treatment of psychological problems.

Hospitalisation

Parameters used in assessing the need for hospitalisation (usually patients are seen in clinic every 2–3 months) include decreasing weight (or poor appetite), diminished exercise tolerance or deteriorating lung-function test results, increased cough and sputum production. School holidays are usually chosen (if possible), as this interferes less with lifestyle, although the reality of hospital bed shortages often means that patients are admitted when a bed is available rather than when it is convenient to the child.

Treatment of lung disease

The focus of CF treatment over the next decade will be the prevention of lung disease.

Pseudomonas can be eradicated in 77% of those treated aggressively after a single treatment cycle. Early intervention is essential, before FEV₁ decline. Optimal use of proven medications to assist chest clearance (Pulmozyme, hypertonic saline, mannitol), anti-inflammatory therapy (include the macrolide azithromycin) and segregating patients with highly transmissible pathogens (MRSA, B. cepacia) will continue to be very important. An Australian 10-year bronchoscopy and CT scans in CF study (completed in December 2009) has shown that at 5 years, structural lung disease is almost universal, although nutritional status and lung function are mostly normal. Two thirds of children have gas trapping on CT by 12 months of age, and 40% have bronchiectasis by age 4. The median age of acquisition of Pseudomonas is 26 months, early acquisition being a known risk factor for bronchiectasis.

CF microbiology: ‘old’ established and ‘new’ emerging pathogens

The microbiology of lung pathogens dictates the usual treatment plans. Initially, the main organisms encountered are Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, P. aeruginosa non-mucoid (probably the cause of at least 30% of exacerbations in children under 2 years of age) and mucoid strains of P. aeruginosa (in >50% of CF patients). B. cepacia infection may be associated with rapidly progressive lung disease. Approximately one third of CF patients have precipitating antibodies to Aspergillus fumigatus, and two thirds have positive skin tests for this. Infection-control issues are important. Cross-infection must be minimised, avoiding the risk of transmission of B. cepacia or P. aeruginosa between infected and non-infected patients. Some clinics cohort by strain of P. aeruginosa as well.

The above pathogens have been recognised for decades in the CF population, and could be termed ‘old’ organisms.

There are now emerging newer pathogens:

MRSA (methicillin-resistant Staphylococcus aureus). This can be associated with a rapid decline in lung function. This can be treated early with clindamycin and rifampicin, given intravenously whenever admitted to hospital.

Stenotrophomonas maltophilia. This is an aerobic Gram-negative organism, aquatic, and previously classified in the genus Pseudomonas. This can be treated with oral antibiotics: trimethoprim with sulfamethoxazole (TMP-SMX).

Alcaligenes xylosoxidans.This is an aerobic Gram-negative bacillus. It can respond to piperacillin and ceftazidine.

Atypical mycobacteria. These can colonise, or actively infect. Should look for signs of disease before treating; can repeat sputum cultures, and perform chest X –ray (CXR) or CT scan of lung fields.

Fungi: Aspergillus. Around 30% CF patients may be colonised. Should look for signs of disease features of ABPA (see below), such as wheezing, positive IgE, positive skin test, and CXR consistent with ABPA.

Fungi: Scedosporium apiospermum. Poor sensitivity to antifungal drugs. Similar to Aspergillus, it is the second commonest filamentous fungus in CF patients (after Aspergillus). It is a saprophyte, obtaining nutrition by assimilating decaying organic matter. Its presence may prevent transplant.

Antibiotics

The following is a general guide. Intermittent oral antibiotics can be used for exacerbations of disease with minimal respiratory symptoms. Ciprofloxacin, plus nebulised antibiotics such as tobramycin or colistin, may be used in patients with chronic P. aeruginosa infection. Continuous oral antibiotics may be appropriate with persistent sputum production or deteriorating lung function. Nebulised antibiotics can be cycled one month on, one month off, or alternate tobramycin/colistin month by month. Intravenous (IV) therapy is reserved for a sick child or deterioration in status on appropriate home treatment, or specifically for eradication-type therapy, if that is required. Occasionally, regular admissions are booked for children with very severe lung disease.

1. Sputum cultures do reflect lung flora in CF (but only in children who can produce sputum easily). Oropharyngeal cultures have poor sensitivity and positive prediction (around 55%), and better specificity and negative prediction (around 85%).

2. Choice of antibiotic for hospital treatment is usually an antipseudomonal penicillin (e.g. ticarcillin with clavulate, piperacillin) and an aminoglycoside (e.g. tobramycin), plus oral flucloxacillin. Cephalosporins such as ceftazidime, nalidixic acid derivatives and polymyxins may also be used.

3. Dose of antibiotic. Abnormal metabolism, and rapid excretion, of antibiotics occurs. ‘Double dose’ antibiotics are needed, especially aminoglycosides (e.g. tobramycin, gentamicin). Adult-dose IV antibiotics can be given from 7 years of age, in general, but this does depend on the antibiotic. As patients get older, the tobramycin dose may need to be wound back. Aminoglycosides are given as single daily doses.

4. Route of antibiotic:

(a) Intravenous (IV). Issues include the problem of venous access: peripheral lines (standard and ‘long’) versus implantable devices, or venous access ‘ports’ (Infuse-A-Port, Port-A-Cath). Complications of ‘ports’ or central venous lines can include thrombosis, infection, haemorrhage, embolism, loss of venous access and needle phobia.

(b) Inhaled. Many units use nebulised antibiotics (e.g. gentamicin, colistin, ticarcillin, tobramycin) at home in some children. Their use is associated with a dramatic decrease in hospital admissions. Disadvantages include allergy, resistance, expense, bronchoconstriction (infrequent) and time required for nebulisation (compliance problem). It is important to have the appropriate nebuliser device for the drug. There are three types of nebuliser; ultrasonic, jet (including breath-assisted open vent and breath-actuated types) and a range of newer ‘vibrating mesh’ nebulisers; there are many different types on the market, some only available when the patient is taking a particular antibiotic (e.g. the I-neb with Promixin [colistimethate], where it only operates where there is a microchip/disc programmed to the drug Promixin; other discs are available to allow nebulisation of other medications, such as hypertonic saline, salbutamol, rh-DNase and tobramycin). Improved technology has shortened the period of time and inconvenience of nebulising significantly.

(c) Oral. For mild-to-moderate exacerbation of lung disease (outpatient management), directed against the most likely (non-pseudomonal) flora. Cotrimoxazole or amoxycillin with clavulanic acid can be used. If no improvement occurs with the first choice, change antibiotics based on sputum sensitivities. Some centres give oral flucloxacillin prophylactically in the first year.

Ciprofloxacin, an oral antipseudomonal quinolone, can be used in older children for a short period, usually 2–3 weeks. However, resistance can develop quickly. Longer courses are used for the eradication of P. aeruginosa, usually 1 month of oral ciprofloxacin plus 2 months of nebulised colistin. Any of these modes of delivery can be used at home.

Most exacerbations of chest disease are probably due to viral infections.

Some patients take regular azithromycin, which can decrease the number of chest exacerbations requiring IV therapy, and also has anti-inflammatory properties. It can be used as an adjunct treatment, particularly with the aim of reducing the number of days of IV antibiotic use required. It has a long intracellular half-life and can be given three times a week.

Some older drugs have been given newer formulations: aztreonam lysinate inhaled has become available (uses an eFlow Rapid Nebuliser); tobramycin has become available as dry powder capsules; ciprofloxacin solution has become available, and once daily Amikacin nebulised is available.

Eradication of Pseudomonas aeruginosa

P. aeruginosa produces alginate biofilms, which protect it from antibiotics and neutrophils. Having P. aeruginosa by 2 years of age is highly correlated with later bronchiectasis. To eradicate it, the patient can be admitted for 2 weeks’ intravenous ticarcillin and tobramycin, or ceftazidine and tobramycin, and then oral ciprofloxacin and nebulised colistin or nebulised tobramycin for 1 month.

Chest physiotherapy

Parents and patient are educated in home physiotherapy from the time of initial diagnosis. ‘Classical’ physiotherapy comprises postural drainage, percussion and vibration, and requires the assistance of a partner. It is usually performed for 10–20 minutes, once or twice a day. It is most useful in children with chronic sputum production, but its value is uncertain in older children with ‘dry’ chests. It remains useful in acute exacerbations of disease.

Other methods encourage independence and may be used in combination with the above. Positive expiratory pressure (PEP) masks are used by several centres. The resistance of the mask is variable; the appropriate value can be chosen by lung-function testing to document the highest increase in forced vital capacity achieved. It is usually used for 10 minutes at a time, once or twice a day. Forced expiratory technique can be taught from 8–9 years. Exercise should be encouraged from a very young age and especially encouraged to continue in the teenage years.

Nebulised treatment

Bronchodilators, saline, hypertonic saline and mucolytics may be used, and are best given before chest physiotherapy. Antibiotics, cromolyn or corticosteroids, when used, are best given immediately after physiotherapy. Hypertonic (6%) saline can achieve improvement comparable to that with dornase alpha (see below).

Bronchodilator treatment

Increased bronchial reactivity is found in 40–75% of CF patients. Standard anti-asthma treatment may be used, including inhaled (nebulised or pMDI) beta-2 agonists (e.g. salbutamol). Note that the condition of some patients can deteriorate following bronchodilators, with a loss of airway wall tone, and dynamic airway compression.

Anti-inflammatory treatment

Long-term use of oral corticosteroids (OCS) and of ibuprofen has been shown to slow the progress of CF. Azithromycin is used for its anti-inflammatory effects. Studies on inhaled corticosteroids (ICS) are somewhat contradictory; a retrospective analysis of 2978 patients with CF receiving inhaled steroids suggested there may be a lessening in the rate of lung-function decline, whereas a Cochrane review of 506 adults and children suggested that inhaled steroids do not improve lung function and, furthermore, that high-dose fluticasone might slow growth in children. Asthma should be appropriately managed.

Mucolytic treatment: Dornase alfa (recombinant human deoxyribonuclease 1) (Pulmozyme)

Dornase alfa (rhDNase 1) is an enzyme that cleaves extracellular DNA and decreases the viscoelasticity of purulent lung secretions. It is used in children with chronic suppurative disease or obstructive disease, with forced vital capacity (FVC) at least 40% of predicted. It is impossible to predict who will respond to it. A small number of patients may get worse or show no change, and a third will show a marked improvement in lung function. In most cases, the response can be judged within 2 weeks of starting treatment. Given once daily through an approved nebuliser (not ultrasonic; preferably with a mouthpiece), a 1-month trial is used to assess the change in lung function. It is stopped if FEV₁ decreases, or there is less than 10% improvement in FEV₁. There are few long-term data regarding any influence on the overall progression of the disease. Many patients may feel symptomatically better, but hospital admission rates are not reduced. It has no place in acute respiratory tract infections.

Alternative therapies

These are frequently used, often cost large amounts of money and can be dangerous. Occasionally, unscrupulous operators have tried to sell household bleach as something that kills germs and can be nebulised. There was a fad for nebulising tea tree oil as well. Silver is used by many, and can cause severe discolouration of the skin and anaemia. It is always worth asking about alternative therapies.

Allergic broncho-pulmonary aspergillosis (ABPA)

This is difficult to diagnose in CF, as the features of ABPA (CXR findings, increased serum immunoglobulins) occur in CF, except for IgE. A high IgE level is suggestive of ABPA if other features are present. ABPA can occur in progressive stages: acute stage (upper- and middle-lobe infiltrates, eosinophilia, IgE level very high, prednisolone responsiveness); remission (after 6 months; normal CXR, no prednisolone); recurrent exacerbation stage (recurrence of infiltrates, eosinophlia, IgE elevated, prednisolone responsiveness, if steroid resistant respond to omalizumab); steroid-dependent asthma stage (chronic obstructive airways disease, responds to prenisolone or inhaled steroids, or omalizumab); fibrotic stage (diffuse airway disease, with obstruction and fibrosis, variable CXR, poor response to steroids; this phase can be terminal). Treatment is stage dependent. Agents used may include: prednisolone; methylprednisolone pulses; antifungal agents (the ‘-conazoles’—itraconazole, voriconazole or posaconazole); anti-IgE agent (omalizumab); G-CSF (granulocyte colony-stimulating factor); GM-CSF (granulocyte–macrophage colony-stimulating factor); interferon; TNF (tumour necrosis factor); therapeutic bronchoscopy/surgery. For acute stage, management often includes steroids and antifungal agents for 6 months. Progress may be monitored by IgE levels. ICS may ease the asthma symptoms.

Haemoptysis

This is a common complication of moderate to severe lung disease. No specific treatment is needed for minor haemoptysis; treat the infection and reassure the child. Any haemoptysis over 15–20 mL probably warrants hospital admission, and may need oxygen, vitamin K or transfusion with larger bleeds. Massive haemoptysis (over 300 mL blood loss in 24 hours, with falling haematocrit and hypotension) can occur from bronchial collateral vessels (usually upper lobe). Treatment includes upright position, stopping chest physiotherapy, arranging cross-match, treating with intravenous antibiotics, vitamin K and reassurance. Bronchial artery embolisation or, in severe cases with respiratory failure, intubation with balloon tamponade and emergency lobectomy, may be needed. For frequent life-threatening haemoptyses, lung transplantation may be needed.

Pneumothorax

A complication of severe lung disease. Generally, the more severely affected lung collapses. It is a poor prognostic indicator (75% die within 3 years), recurrence is common.

Acute management: oxygen—a conservative approach if possible, but each case should be treated on its merits. The prospect for future lung transplantation is adversely affected by more aggressive intervention, such as tube thoracostomy (can scar the pleura, and may also cause bronchopleural fistula), chemical pleural sclerosis or surgical pleural abrasion. Needle aspiration may bring symptomatic relief.

Cor pulmonale or right heart failure

This is a poor prognostic indicator (median survival 6 months). Treat hypoxia with home nocturnal oxygen. Diuretics may be needed. Treat any infection. BiPAP can be used in patients with respiratory failure to maintain them and avoid heart failure. Cor pulmonale can resolve with lung transplantation (see below).

Lung transplantation

CF is the most common indication for paediatric lung transplant. CF does not re-occur in transplanted lungs. Bilateral sequential single-lung transplantation is now the operation of choice, the sole option for long-term survival of terminal patients. The mainstem bronchus and pulmonary artery are connected by end-to-end anastomoses; the two pulmonary veins from each lung are harvested intact with a patch of the left atrium of the donor, and then each left atrial patch is sewn to the recipient’s left atrium. This is performed using cardiopulmonary bypass. Living-donor lobar transplantation (LDLT) is another option, which is rarely performed because of technical and ethical complexities: it requires two donors, each undergoing a lower lobectomy to provide a right and left lower lobe to serve as right and left lungs for the recipient; for adolescents taller than 152 cm, the donors need to be tall enough to provide adequate lung tissue.

The main indications are: life expectancy less than 2 years (usually corresponds to FEV₁ below 30% of predicted), quality of life impaired (oxygen dependent at home, doing nothing) or frequent life-threatening haemoptysis (initial attempted control will be by bronchial artery embolisation). Other indications for referral to a transplant unit include hypercapnic respiratory failure, exacerbation of lung disease sufficient for ICU care, increased frequency of pulmonary exacerbations requiring antibiotic therapy, and recurrent or refractory pneumothorax. The ideal clinical status includes no major systemic disease (and preferably no surgical procedure to the chest), optimal nutrition (between 70% and 130% of ideal body weight), not on a ventilator and on no more than a low-steroid dose (5 mg or less of prednisolone per day), adequate psychological status, adequate social supports and no major psychiatric illnesses.

There are virtually no contraindications to transplantation. Advice from local tertiary centre transplantation centres should be sought for each case considered. There are, however, areas for discussion in cases with progressive neuromuscular disease, previous malignancy in the last 2 years, pleural space disease, active infection with Aspergillus, Mycobacterium or multiply resistant bacteria, such as some strains of B. cepacia, high-dose steroids, gross malnutrition and some psychosocial areas (non-compliance with recommended treatment, major psychoaffective disorders). Donor–recipient matching is based on ABO blood group incompatibility, CMV antibody status and the size of the thoracic cage. Immunosuppressive regimes may include a calcineurin phosphatase inhibitor (e.g. tacrolimus), a purine synthesis inhibitor (e.g. mycophenolate mofetil) and prednisolone.

Complications fall into three groups:

1. Immediate phase (first few days post-transplant). Subgroups include the following:

(a) Hyperacute rejection (due to prior exposure to foreign tissue antigens, complement-mediated vascular injury and thrombosis that can lead to loss of the graft; rare).

(b) Early graft dysfunction due to ischaemic injury during harvesting and reimplanting the lungs; occurs in 13–35%; manifests as pulmonary oedema (non-cardiogenic), with decreased lung compliance and poor oxygenation; managed supportively (ventilation, extracorporeal membrane oxygenation [ECMO], nitric oxide).

(c) Surgical complications (airway and vascular anastomoses can break down; bleeding from vascular anastomoses or chest cavity can be persistent; vocal cord and hemidiaphragm paresis or paralysis can occur, but usually resolve in a few months; early re-operation needed in around 10% of cases).

(d) Infection of pulmonary allograft, secondary to poor mucus clearance (impaired cilial function), poor cough (pain), impaired diaphragm function (phrenic nerve injury), low IgG (from cardiopulmonary bypass) and immune suppression.

2. Early phase (first few weeks post-transplant). Subgroups include the following:

(a) Acute rejection (common; may present with dyspnoea, fever, hypoxia, abnormal chest X-ray with perihilar infiltrates or effusions, or obstructive-pattern spirometry); diagnosed on bronchoscopy, bronchoalveolar lavage, transbronchial biopsy; treated with high-dose IV methylprednisolone; if persists, treated with a mono- or polyclonal T-cell antibody preparation (e.g. antithymocyte globulin [ATG]).

(b) Infection: CMV—treat with valganciclovir; bacterial lower respiratory tract infection—treat with IV antibiotics.

(c) Side effects of surgery (narrowing at suture line of airway anastomosis): treated with bronchoscopic balloon dilatation; distal intestinal obstruction syndrome [DIOS] (see below); arrhythmias, usually atrial, from interference with integrity of muscle along suture lines, where donor atrial patches with pulmonary veins are attached (see above).

(d) Side effects from medication (triple immunosuppression with calcineurin phosphatase inhibitor [e.g. tacrolimus], a purine synthesis inhibitor [e.g. mycophenolate mofetil] and prednisolone; for discussion of these drugs, see other sections on organ transplantation—e.g. renal, liver, heart).

(e) Seizures (can be due to tacrolimus or cyclosporine, secondary to cerebral vasoconstriction).

(f) Hypertension (in 36% of cases at 1 year, 71% at 5 years; may be due to tacrolimus or cyclosporine, or steroids): treat with calcium channel blockers or angiotensin-converting enzyme (ACE) inhibitors.

(g) Diabetes mellitus (occurs in 20% at 1 year, 28% at 5 years) can be precipitated by steroids or tacrolimus.

(h) Renal dysfunction (hypomagnesaemia, renal tubular acidosis, chronic renal insufficiency; more common in re-transplantation).

3. Late phase (months post-transplant). Subgroups include the following:

(a) Bronchiolitis obliterans (OB) (the main reason that lung transplantation is not as successful as solid organ transplantation); treatment difficult—tried treatments include ATG, cyclophosphamide, methotrexate, total lymphoid irradiation; better management of rejection has led to improved rates of OB.

(b) Malignancy (most often post-transplant lymphoproliferative disorder (PTLD); in 6.5% at 1 year, 8.2% at 5 years): treatment—reduced immunosuppression plus CD20 antibodies.

(c) Renal failure (due to calcineurin inhibitors and other nephrotoxic drugs [e.g. aminoglycosides]; occurs in 7.7% at 1 year, 26% at 5 years).

Post-transplant, any acute respiratory illness or acute febrile illness should be investigated and treated aggressively. One needs to be aware that many medications (anticonvulsants, macrolides, antifungals) can interact with the main immunosuppressive agents used (tacrolimus, cyclosporine); MIMS or a similar reference should be checked each time a new medication is contemplated.

The drug levels of antirejection therapy such as cyclosporine must be closely monitored, as inadequate pancreatic enzyme supplementation and erratic absorption of medication can decrease the levels, allowing rejection to occur. If there are many episodes of graft rejection within 2 months of lung transplantation, there is a high frequency of post-transplant lymphoproliferative disease (PTLD).

Females may require transplantation earlier than males, as they have a median survival of 28 years, compared to males’ 44 years. Suggestions are that females should be assessed and transplanted at a different lung function compared with males, but this varies with different centres. The survival rate approaches 87% at 1 year, 70% at 3 years and 60% at 5 years. The three most significant factors for poor outcome are repeat transplant, mechanical ventilation at transplant and coexistent congenital heart disease. The three main causes of death are early graft dysfunction (most deaths in the first 30 days post-transplant), infection (first year post-transplant) and bronchiolitis obliterans (beyond the first year post-transplant, for cadaveric transplant recipients; rare in LDLT). Preoperatively, a 2-week assessment in hospital in necessary. The usual age has been around 17–19 years. The rate-limiting factor for this treatment is the scarcity of donor organs. To overcome this, as well as LDLT, reduction surgery and xenograft transplantation from genetically engineered porcine donors have been developed. Concurrent heart and lung transplants have been performed in patients with severe CF lung disease and significant associated cor pulmonale. A study reported in 2007, based on a retrospective cohort study of 514 children with CF on a transplant waiting list, of whom 248 had lung transplants, estimated that only five patients would clearly have improved survival from lung transplantation, inferring that lung transplantation was not necessarily associated with an improved survival in children. Some 50% of lung-transplanted patients have obstructive lung disease in 4 years. Patients can have re-transplants.

End-of-life care

Limited organ availability means that some patients die waiting for a transplant. End-of-life discussions can be held too close to the time the patient dies. ‘End-of-life’ refers to the period of time when the patient’s clinical state is deteriorating relentlessly, and death is likely within a limited time frame (usually 2 years); at this juncture, consideration is given to transplantation and palliative care. A discussion regarding potential transplantation, and its requisite assessments/work-up, allows an opportunity to bring up end-of-life issues at that point, rather than postponing consideration of palliative care and end-of-life issues.

Invasive respiratory support

The most appropriate indications for such support are acute reversible conditions such as pneumothorax-precipitating respiratory failure (while waiting for the lung to reinflate after initiating drainage), massive haemoptysis (while awaiting bronchial artery embolisation) or postoperatively, after major surgery.

Non-invasive positive pressure ventiliation (NPPV)

NPPV has been reported as being effective in treating impending respiratory failure (in the context of upper abdominal surgery or severe acute pulmonary exacerbation) and avoiding intubation. NPPV also has been reported as improving airway clearance and gas exchange during sleep in patients with CF, and improving respiratory muscle performance and decreased oxygen desaturation episodes during chest physiotherapy.

Immunisation

As well as routine vaccination, many paediatric respiratory units actively encourage influenza vaccination, particularly for very young patients and for those with severe lung disease. Illnesses resembling influenza may be treated with antiviral agents; for example, oseltamivir oral preparation makes it suitable for children from 12 months of age. Pseudomonas vaccines are being trialled.

Burkholderia cepacia infection

This can be associated with rapid decline in lung function, and increased mortality. It is now recognised that this organism can survive in respiratory droplets on environmental surfaces for prolonged periods, such as in CF clinics. Person-to-person spread occurs. Patients with B. cepacia infection are usually seen separately in outpatient clinics and are nursed in isolation as inpatients. The organism is found in the environment and sporadic infections are seen. It is important to strain type B. cepacia and to ensure that there is no person-to-person spread; vigilance is required with all aspects of care, including healthcare professionals’ hand washing, equipment use and cleaning in pulmonary function laboratories.

Sinonasal disease

Most children with CF have sinonasal disease, but it is underreported. On CT scan, 92–100% of CF patients have chronic rhinosinusitis, the average age of onset being 5–14 years. Nasal polyps are seen in 30–50% of CF patients, versus 0.1% of non-CF/normal children; of these in CF patients, only around 60% are symptomatic. The history for sinonasal disease may include nasal obstruction, mouth breathing, cough, nasal discharge, post-nasal drip, headache, facial pain, hyposmia, anosmia, poor sleep, snoring, limited activity, hoarseness and halitosis. Examination findings may include congested turbinates, post-pharyngeal oedema, nasal polyps, medialisation of the lateral nasal wall and craniofacial distortion. Nasal polyps can be managed medically, with oral antibiotics, nasal toilet with normal saline irrigation, irrigation with tobramycin or nasal inhalation of pulmozyme.

Only in exceptional circumstances will surgical treatment of polyps go ahead, when refractory to any other treatment, because of the attendant risks of anaesthetising a patient with CF (these patients can get severe mucus plugging of their airways during anaesthesia, especially when intubated), the possible complications (especially injury to surrounding structures: CSF leak, meningitis, medial rectus damage, optic nerve damage, blindness, cerebral injury, orbital bleeding) and because surgical treatment is not a cure, but a symptomatic treatment only, and up to three quarters can need surgical revision within 2 years. The usual surgery performed is endoscopic sinus surgery comprising polypectomy, wide middle meatal antrostomies, anterior and posterior ethmoidectomies, and removal of polypoid disease in the frontal recess. Postoperatively: saline, steroids, antibiotics and clinic follow-up for division of synechiae (between inferior turbinates and septum).

Treatment of gastrointestinal disease

Pancreatic insufficiency (PI)

The degree of PI is determined by the specific nature of the CF mutation. Certain mutant alleles are associated with PI or pancreatic sufficiency (PS). Fat absorption improves from about 60% without therapy, to 85–90% with pancreatic enzyme replacement therapy (PERT). Dosage regimens have been revised since recognition of the association between high-strength PERT and the development of fibrosing colonopathy.

PERT doses should be derived from a ratio of lipase units per gram of dietary fat ingested; an upper limit of 10,000 units of lipase per kilogram per day has been suggested.

Pancreatic enzyme supplements contain lipase, amylase and proteases. Most units use enteric-coated microspheres. Three preparations are available in Australia: Cotazym-S (capsules contains 10,000 units of lipase), Creon (capsules can contain 5000, 10,000 or 25,000 units of lipase) and Panzytrat 25000 (capsules contain 25,000 units of lipase). The amounts of protease and amylase also vary between preparations. Adjusting PERT to the fat content of foods ingested can lead to increased absorption of fat, despite no change to the total capsule number. PERT guidelines for infants suggest 500–1000 units of lipase per gram of dietary fat, starting with a minimum dose (2500 units of lipase per 120 mL formula/breast feed), increasing the dose according to weight gain and bowel signs. For children, the guidelines suggest 500–4000 units of lipase per gram of dietary fat. For the average child, whose requirement is around 5000 units of lipase per 3–4 g of fat, this is roughly one 5000-lipase-unit capsule per kilogram body weight per day. Adjustment should be in concert with medical staff, not independently. For younger children, the contents of the capsules should be mixed with acidic fruit gel or yoghurt, not chewed, and the oral cavity should be cleared with a finger after the feed to remove residual microspheres, as enzymes work for up to 30 minutes after ingestion. Older children and adults should swallow the capsules whole just before or during eating. PERT should be given with all foods and fluids that contain fat. The aim is for normal growth and normal stools.

Some patients appear refractory to PERT (i.e. stool fat output persistently above 25% of fat intake), related in some to duodenal acidity. Treatment for these patients may include gastric acid suppression with antacids, H₂ receptor blockers (e.g. ranitidine), proton pump inhibitors (e.g. omeprazole) or prostaglandin analogues (e.g. misoprostol) to aid fat digestion. An alternative pancreatic enzyme preparation may be tried, as dissolution profiles may vary, or preparations may be given at the start of the meal, for earlier onset.

Cystic fibrosis related diabetes (CFRD)

CFRD is the most common co-morbidity in CF, increasingly seen due to the increasing lifespan of CF patients: it occurs in 9% of 5–9 year olds, 26% of 10–20 year olds and 50% of patients by 30. CFRD can be a fluctuating diagnostic state; CFRD can occur with or without fasting hyperglycaemia; the usual CFRD developmental path begins with early, variable intermittent postprandial hyperglycaemia, followed by impaired glucose tolerance, then diabetes without fasting hyperglycaemia (plasma glucose <7 mmol/L fasting, but 2 hour glucose level >11.1 mmol/L), followed by diabetes with fasting hyperglycaemia. CFRD increases the mortality rate in CF sixfold, and the prediabetic state is associated with increased morbidity. CFRD is treated with insulin, not oral hypoglycaemic agents.

CFRD tends to develop insidiously. Clues may include delayed puberty, failure to gain weight/decreased growth velocity, unexplained deterioration in lung function, or the more obvious presentation of polyuria and polydipsia. Microvascular complications occur, but are rare before 10 years duration with CFRD; they include microalbuminuria (14%), retinopathy (16%), gastropathy (50%) and neuropathy (55%). CFRD is linked to the common delta-F508 mutation. The pathology is fibrosis and fatty infiltration of the pancreas, which disrupts the islet architecture, causing insulin deficiency (which can be severe but not absolute); this process also can cause impaired glucagon secretion. Insulin resistance occurs because of decreased peripheral glucose uptake and inadequate insulin suppression of hepatic glucose production.

Several aspects to CFRD are quite different to both type 1 and type 2 diabetes. Calorie restriction is contraindicated, as a high-calorie high-fat diet is indicated in CF. Diabetic ketoacidosis (DKA) is rare, due to persistence of endogenous insulin production and impaired glucagon response. CFRD can first present when insulin resistance is increased (e.g. during immunosuppression post-transplant with tacrolimus usage, with steroid treatment, with increased calories from nasogastric overnight feeds). It is more severe with coexistent liver disease. There may be a gender difference in survival: one study reported CFRD with median survival 48 years in males but 31 years in females; however, this gender difference was not seen in another study. HbA1C is unreliable in CFRD.

The insulin regime in CFRD is managed along standard lines used for type 1 diabetes, but particular difficulties can occur with concomitant corticosteroid usage and dietary requirements. Overnight feeding may require isophane and regular insulins to cover. Basal insulin requirements can increase fourfold with acute illness, but they also drop rapidly once the intercurrent acute illness is resolved. For further discussion on insulin, see the long and short cases on diabetes in Chapter 7 (Endocrinology).

Nutrition

A high-energy diet is recommended. CF patients require approximately 120% of normal energy requirements because of increased energy use (due to the effort of breathing, and infection), decreased protein synthesis with acute exacerbations of chest disease, nutrient loss with malabsorption, anorexia and raised basal metabolic rate. Less than optimal nutrition may lead to poor growth, impaired respiratory function and decreased exercise tolerance.

Diet should be liberal, with a high intake of a variety of foods, rich in fat (extra margarine, butter, ice-cream, cream), sugar (unless diabetic), salt, milk products, protein foods, cereals and bread. Breastfeeding is desirable for babies with CF; soy milks are not recommended.

In advanced lung disease, with loss of weight and anorexia, despite optimal oral intake, long-term supplementation of nutrition may be appropriate by invasive means (e.g. nasogastric tube or gastrostomy). Caloric supplementation may result in improvement in growth and well-being. Nutritional and respiratory status influence each other; if one should deteriorate, so will the other.

Vitamins

Patients are at risk of deficiencies of fat-soluble vitamins A, D, E and K, especially at diagnosis. Children under age 2 can take a liquid preparation such as Penta-vite liquid multivitamins (which, curiously, contains seven vitamins: vitamin A, thiamine [B1], riboflavin [B2], nicotinamide [B3], pyridoxine [B6], vitamin C and cholecalciferol [vitamin D3] 0.45–0.9 mL daily), plus a vitamin E (alpha tocopherol) preparation such as Micelle E 0.2 mL daily, and vitamin K (phytomenadione) 2.5 mg daily. An alternative is VitABDECK 1–2 mL daily. Preschoolers take Pentavite chewable tablets, plus Micelle E 0.4 mL daily, and Vitamin K 5 mg twice weekly. Again an alternative is VitABDECK two capsules daily; additional Micelle E or Vitamin K may be needed. School-age children can take Vitamin A 5000 units daily, Vitamin E 100 units daily, and Vitamin K, 10 mg twice a week. The aforementioned are the recommendations of the Cystic Fibrosis Standards of Care, Australia, 2008. Recommendations vary on vitamin supplementation in other units in other countries.

Salt

Many units use oral rehydration solutions (e.g. Glucolyte or Gastrolyte) as a source of salt, as fluid, as well as salt, is useful, particularly in younger children. Guidelines for recommended amounts of salt are as follows:

1. Under 6 months: 0.5 g/day (1 g/day in hot weather).

2. 6–12 months: 1 g/day (1.5 g/day in hot weather).

3. 1–5 years: 2 g/day (3 g/day in hot weather).

4. Over 5 years: 3 g/day (4 g/day in hot weather).

Salt replacement may be needed several times a day in hotter weather. Parents can add salt to food, and offer their children salty snack foods. In infants, salt can be given as oral rehydration solutions, or as pinches of salt added to the bottle. As children get older, they may switch to salt tablets with added drinks. The fluid component is important to reduce DIOS.

Treatment of other complications

Cystic fibrosis related bone disease (CFR-BD)

Musculoskeletal complications are increasingly recognised with longer life span. The best predictors of bone health are nutritional status and severity of lung disease in early adolescence:

• Hypertrophic pulmonary osteoarthropathy (HPOA) is the most common disorder (it occurs in 2–7% patients with CF). It is characterised by digital clubbing, and long-bone and joint pain (especially wrists, knees and ankles), worsened by pulmonary exacerbations. The aetiology remains unclear. Bone scan can detect HPOA early. Management includes optimising pulmonary care and aggressive treatment of exacerbations. Non-steroidal anti-inflammatory drugs (NSAIDs) may relieve discomfort.

• Kyphosis with an angle over 40° occurs in over 75% of adult female CF patients, and around one third of adult male patients. Both HPOA and kyphosis are associated with deteriorating lung function, and are seen as markers of a poor prognosis.

• Low bone mass is common, despite supplementation with vitamin D, calcium and PERT. The bone mineral density decreases and the fracture risk increases with increasing age. Osteoporosis and crush fractures can lead to significant back problems. Rib fractures are also reported. Severe bone loss occurs in transplant patients.

• CF episodic arthritis usually presents with recurrent (non-destructive) mono-articular involvement or a symmetrical polyarthritis. It can be managed by standard therapy (NSAIDs or aspirin). Glucocorticoids may be required, orally or intra-articularly. It has been observed that antibiotic therapy for lung disease can improve joint symptoms. Eruptions resembling erythema nodosum may occur in association with it.

• Rheumatoid arthritis has been reported, and treated along standard lines.

• Ciprofloxacin-induced arthralgia is treated by stopping the drug.

Growth and recombinant human growth hormone (rhGH)

Poor linear growth and inadequate weight gain are very common, and adults with CF have lower than average final adult heights. Poor weight gain and worsening of clinical state are well known. It has been hypothesised that improved linear growth can allow greater lung mass, leading to improved lung function. Many studies of rhGH in children with CF have shown significant improvement in height velocity, weight velocity, bone accumulation, forced vital capacity and exercise tolerance.

Adolescence and fertility

Females with CF are mildly subfertile (related to suboptimal body weight, thick cervical mucus, low body fat and associated oestrogen deficiency). Many pregnancies are successful, although pregnancy can be associated with risk of cardiorespiratory failure and fetal loss; however, the only contraindication is cor pulmonale. Tolerance of pregnancy depends on the severity of lung disease, and is better tolerated in those with milder disease and in those with a certain ideal body weight before conception. Risk factors for a poorer outcome of pregnancy include FEV₁ < 50% predicted, undernutrition and CFRD.

The choice of contraception can be difficult and should be individualised. Barrier methods such as condoms are very effective. Liver disease is a contraindication to the use of the combined oral contraceptive pill. Implanon (etonogestrel) implants and 3-monthly Depo-Provera (medroxyprogesterone acetate) have been used for contraception, but many units recommend avoidance of Depo-Provera because of concerns about adverse effects on bone health in the long term. Oral contraceptives have been avoided in adolescent females, because frequent use of different antibiotic therapies may affect drug levels and effectiveness, and patients may have liver disease, but oral contraception remains the commonest form used in adult women with CF. The hormone levels of the OC pill are not affected by concomitant ingestion of ampicillin, ciprofloxacin, clarithromycin, doxycycline or roxithromycin. Oral contraceptives are also used for medical/hormonal purposes, such as acne or painful menses.

With increased survival, many CF patients request genetic counselling and fertility assessment. Genetic screening of partners detects around 90% of carriers. Females with CF can overcome difficulties with conception by in-vitro fertilisation techniques.

Males with CF usually have congenital bilateral absence of the vas deferens (CBAVD), but the resultant infertility can be managed by having spermatazoa retrieved by direct aspiration from the head of the epididymis, then intracytoplasmic sperm injection (ICSI) into an oocyte obtained by egg harvesting.

Drug allergies

In adult CF clinics, some 35% of patients with CF eventually will have an allergy to more than one class of anti-Pseudomonas antibiotic, and 1 in 8 will have allergy to two or more beta lactam-containing antibiotics. This is due to cumulative exposure.

Common management issues

What should the patient know about the illness?

Most patients are diagnosed through neonatal screening, so that the parents receive education about the condition. As children get older, simple explanations are required to explain why they require physiotherapy and medications. Fertility should be discussed at around 13–17 years of age, explaining infertility to the boys and implications of pregnancy to the girls. With acceleration in the ease of information retrieval, most children and parents will have obtained much information from the internet and will be asking challenging questions regarding these issues earlier than in the past.

How much should school/peers be told?

School should be told about the diagnosis, the need for exceptions to school rules (e.g. running late for class due to treatment at home, running to toilet, being exempt from sport) when necessary, and the need for free access to bronchodilator therapy. Schoolfriends can be supplied with information when they ask, keeping answers simple, but there is little point in trying to keep the diagnosis secret. It is important that the school is aware that if there is more than one patient with CF in the school, the children should not be in the same class, to avoid prolonged contact and the risk of transmission of organisms from patient to patient. It is of key importance that children and parents have a positive attitude to prognosis and ensure adequate education. The majority of children born with CF today will live to adult life, will need to work and may have a family of their own.

When should the patient take responsibility for self-care?

Children can generally manage to swallow their pancreatic enzymes by age 5. Adolescents often start to have some time alone with the doctor during consultations by around age 14 and achieve total self-care by the end of adolescence.

When should the patient transfer to adult care?

The appropriate time is more dependent on maturity and physical health than age. Some units feel the year after leaving school is the appropriate time, with prior introduction to the adult physician. A common problem with transfer is decreased compliance (factors include loyalty, rapport with new doctors, physiotherapists, change in treatment, clinic environment, drug costs and loss of parental supervision). Positive reasons for transfer include recognition of transition to adulthood and patient preference (but a problem can be disease stability at the time). Negative reasons include crowding of paediatric outpatient clinics and disinclination of paediatricians to manage adult problems. Most young people are happy to transfer care when they finish school or if they take on adult responsibilities and behaviours earlier. Many units make the transition to adult care after completion of grade 12. Most patients are happy with this and, although most parents are worried, the doctors and therapists usually have no concerns.

Is modification of current medical treatments warranted?

Alternate daily oral steroids may impact negatively on growth and bone density, and increase the risk of diabetes, although previously reported positive effects have included increased growth and appetite, decreased infection and increased well-being in some patients. Home intravenous antibiotics using venous access ports had appeared promising, and seemed as effective as hospital antibiotics, but now many studies have shown that home IV treatment may require a longer time on therapy, compared to hospital care, to achieve the same end points. Many units reserve this for patients who are very well motivated and have a lot of support. Home oxygen is useful for later-stage ‘restless’ nights and morning headache with significant oxygen desaturation overnight: this needs assessment (e.g. overnight oxygen saturation monitoring, echocardiography to detect cor pulmonale).

Is lung transplantation an option for this patient?

This is an area to be evaluated in any terminal patient with CF. Bilateral sequential single lung transplantation is the sole option for long-term survival of such patients. See the discussion in the section on the treatment of lung disease.

If there is a second major organ failure, a second organ transplant may be appropriate (for coexistent liver failure, liver–lung transplantation; for coexistent heart failure, heart–lung transplantation). In the past, heart–lung transplant had been considered for cor pulmonale associated with pulmonary hypertension; however, it is now recognised that the right-sided heart dysfunction of cor pulmonale resolves after lung transplantation.

Are the family coping at present?

There may be a need for increased financial and social support. Depending on the state of the child’s illness, there may be a need for grief counselling. This is useful at any of the more stressful times in the parents’ lives, including the initial diagnosis, the next hospital admission, the death of someone else’s child, crisis times (e.g. increased hospitalisation, start of school), antenatal diagnosis and termination of pregnancy, and transfer to adult hospital. Grief reactions can include shock, denial, sadness (e.g. loss of expected healthy child/life span), anger (‘Why me?’) that may be directed at health workers, relief (symptoms have a name), guilt (they transmitted the disease), resentment, anxiety (fear for the future) and somatic problems (e.g. headaches).

Are the parents planning more children?

Discussion must include prenatal diagnosis and the ethical problem of what to do should the result be positive. The education of the parents in the genetic considerations should be explored to prevent misunderstanding (e.g. ‘The next three will be all right because the risk is 1 in 4’).

Obstructive sleep apnoea (OSA)

Background information

OSA is at the severe end of the obstructive sleep-disordered breathing (SDB) spectrum, and is the hypoventilation disorder most likely to be encountered in the examination context. With an estimated incidence of 2%, OSA can occur in children of any age, the peak ages being between 2 and 8 years.

In a long-case format, the patient may well have one of the several underlying conditions, such as craniofacial anomalies, neuromuscular disorders or significant obesity. In addition to disruption of normal breathing and sleep architecture, episodes of partial or complete airway obstruction during sleep may lead to significant neurocognitive, cardiovascular or metabolic morbidities. The pathophysiology is complex (a disorder of anatomy and neuromuscular control of the upper airway), involving increased upper airway resistance (most commonly associated with lymphoid tissue [adenotonsillar] hypertrophy, or mandibular/maxillary narrowing or retropositioning), decreased neuromuscular activation, altered ventilatory control, changed arousal thresholds and other abnormalities of sleep architecture. There is typically repetitive collapse of the pharyngeal airway, intermittent hypercarbic hypoxia (IHH) and recurrent transient arousal; IHH and sleep fragmentation impair sleep restoration. Neurocognitive and behavioural morbidities (learning deficits, inattention and hyperactivity) can be attributed to sleep fragmentation and intermittent hypoxia.

The main two determinants of upper airway patency during sleep are, firstly, the anatomical structure/size of the bony and soft tissues of the airway and, secondly, the tone of the upper airway/pharyngeal dilator muscles (genioglossis is the best studied). Accordingly, various craniofacial syndromes that cause midfacial hypoplasia (Apert, Crouzon, Pfeiffer, Treacher Collins), macroglossia (Beckwith–Wiedemann), relative macroglossia/small pharynx (Down), glossoptosis (Pierre Robin sequence) or short cranial base (achondroplasia; which also causes midface hypoplasia, reduced size of foramen magnum [with potential for cervicomedullary compression] and hydrocephalus) affect the anatomy.

Other conditions causing anatomical impingement on the airway calibre include those that decrease the bony cross-section of the lower face (sickle cell anaemia [via bone marrow hyperplasia], juvenile idiopathic arthritis [via micrognathia from temporomandibular joint involvement]), and those that cause increased airway soft tissue (adenotonsillar hypertrophy, obesity [parapharyngeal fat deposits], mucopolysaccharidoses, airway papillomatosis), collapsible upper airway tissues (Marfan; important to pick OSA, because its presence may increase risk of aortic root dilatation; other contributors to OSA in Marfan syndrome are crowded teeth, high-arched palate and narrowed jaw) or laryngeal/tracheal narrowing (laryngomalacia, subglottic stenosis). Various neurological conditions affect the muscle tone, whether upper motor neurone (cerebral palsy) or lower motor neurone (spinal muscular atrophy, myasthenia gravis, various myopathies).

Selected causes of OSA (including genes responsible if relevant) are as follows (mnemonic COMPACTED BREATHING):

C. Crouzon syndrome (FGFR 2 & 3)/Cervical fusion (Klippel–Feil syndrome)

O. Obesity/Overbite (and other dental anomalies)

M. Marfan syndrome (FBN 1)/Moebius sequence/Myelomeningocoele

P. Pfeiffer syndrome (FGFR 1 & 2)/Prader–Willi (deletion at 15 q11–q13)/Paralysed vocal cord

A. Adenotonsillar hypertrophy/Apert syndrome (FGFR 2)/Achondroplasia (FGFR 3)

C. Cerebral palsy/CHARGE syndrome (via choanal stenosis/atresia)(CHD7)/Chotzen [Saethre–Chotzen] (TWIST gene)

T. Tracheal/subglottic stenosis/Tracheomalacia/laryngomalacia

E. Extra tissue (e.g. fatty infiltration upper airway structures, storage disorders, airway papillomatosis, cystic hygroma [lymphatic malformation], nasal polyps in cystic fibrosis)

D. Down syndrome (normal-size tongue, small pharynx causing relative macroglossia)

B. Burns to head and neck/Beckwith–Wiedemann (11 p15.5) (macroglossia)

R. Rhinitis (allergic)/Robin sequence (hypoplasia of mandibular area before 9 weeks in utero) (glossoptosis)/Repaired cleft lip/palate/pharyngeal flap

E. Endocrine disease: hypothyroidism/hypopituitarism (both can cause decreased muscle tone)

A. Arthritis (juvenile idiopathic arthritis) (temporomandibular joint [TMJ] involvement causing micrognathia)/Arnold–Chiari malformation type II (including in spina bifida)

T. Treacher Collins syndrome (TCOF 1)

H. Haematological disease: sickle cell anaemia/Hallermann–Streiff syndrome (malar hypoplasia, micrognathia with hypoplastic rami and anterior displacement of TMJ, high narrow palate)

I. Inborn errors of metabolism: mucopolysaccharidoses

N. Neuromuscular weakness (spinal muscular atrophy, myasthenia gravis, myopathies)

G. Goldenhar syndrome (craniofacial microsomia; first and second branchial arch syndrome [14 q32])

Diagnosis of OSA

Polysomnography (PSG) is a multichannel recording of several physiological parameters during sleep. It is considered the gold standard for diagnosis of OSA, but diagnostic criteria for the paediatric population are inconsistent.

The following parameters are recorded on PSG (mnemonic SLEEPING OVER):

Polysomnographic criteria for diagnosis of OSA in children: the apnoea hypoxic index (AHI), equal to the average number of apnoeas and hypopnoeas per hour of sleep: greater than one is abnormal (whereas in adults the number cut-off is five) and consistent with the diagnosis of OSA. A minimum oxygen saturation less than 92% is also considered abnormal.

Less time-consuming and cumbersome ‘abbreviated tests’ have been disappointing, as they lack sensitivity. Nocturnal pulse oximetry has a high positive predictive value (over 96%) and a high specificity (over 97%), but a low negative predictive value (under 50%) and a low sensitivity (under 50%). Hence this test is of no utility if it is negative.

History

Despite many studies demonstrating a lack of reliability of history in assessing OSA, it is prudent to take a thorough detailed history, focusing on the three most useful diagnostic symptoms (the three S’s): (1) snoring (especially the majority of nights; breathing pauses/observed apnoeas); (2) snorting (the mechanism of breaking obstructive events, and increased work of breathing); and (3) sleep disturbance (movement to find a better position for stable sleep). Also, the history can be divided into night-time/sleep symptoms and daytime/awake symptoms, and varies somewhat depending on the age of the patient. No particular combination of symptoms and signs can differentiate OSA from primary snoring. Parental impressions of sleep problems do not correlate with sleep study findings (as shown in a study where 57% of 56 children aged 4–63 months with Down syndrome had OSA proved on polysomnography). Similarly, a normal score on an OSA-18 disease-specific quality-of-life questionnaire (OSA-18) does not exclude OSA in children.

Presenting complaint

Reason for current admission.

Symptoms

Night-time/sleep: snoring (duration [how long aware of snoring], frequency [every night, most nights], intensity [loud enough to be heard outside of bedroom], when noticed more [second half of night, as OSA worse during rapid eye movement (REM) sleep, associated with relative hypotonia of upper airways and diminished respiratory drive]), whether documented (tape recording, video recording), quality of breathing (pauses in breathing: duration, frequency (how many per hour), associated inspiratory noises at end of pause), mouth breathing, increased work of breathing (use of accessory muscles of respiration, tracheal tug, intercostal recession, sternal recession, subcostal recession), additional noises (snorting, gasping, choking), associated symptoms (unusual/abnormal sleeping position, hyperextended neck, restlessness, restless legs syndrome [RLS; leg discomfort, motor restlessness, worse at night], period limb movements disorder [PLMD; repetitive flexion of hips, knees, ankles; a PSG diagnosis], sweating, bruxism/teeth grinding, secondary nocturnal enuresis).

In infants, also ask about disturbed sleep with recurrent episodes of crying, whether there is an established day/night cycle, any poor sucking/feeding, any ambulance calls for apparently life-threatening events. In toddlers, ask about whether ‘niggly’ or ‘grouchy’, crying spells, night terrors and witnessed apnoeas. In preschoolers, ask about drooling during sleep, confusional arousals, night terrors, sleepwalking, whether hard to wake up, need for napping and poor eating.

In school-aged children, ask about sleep-talking, insomnia, daytime fatigue, aggression, shyness, depression, low self-esteem, delayed puberty, dental problems (e.g. overcrowded teeth, malocclusion, severe enough to see a dentist/orthodontist). The increase in partial arousal parasomnias (sleepwalking, night terrors), is due to compensatory increase in slow wave sleep in response to sleep fragmentation.

Daytime/awake: symptoms on waking (headache, thirst, jaw pain [from bruxism], stiff neck [from neck hyperextension], mouth breathing, dry mouth, hyponasal speech, nasal ‘congestion’, rhinorrhoea [allergic rhinitis], difficulty swallowing [tonsillar hypertrophy], hearing problems, poor appetite, excessive daytime sleepiness (usually the predominant symptom), taking naps, behaviour problems (excessive disruptive symptoms [easily frustrated, agitated, irritable, aggressive, moody, emotionally labile, impulsive, increased activity], ADHD-like symptoms [poor attention span, academic problems, may have been diagnosed as ADHD, may be taking stimulants], oppositional behaviour, conduct problems, increased somatic complaints [internalised]—sleepiness is associated with attention loss; poor executive abilities reflect hypoxaemia to frontal lobe), neurocognitive difficulties (learning problems, poor school performance, any psychometric testing, IQ score), cardiovascular symptoms (hypertension noted by local doctor or paediatrician—hypoxia and microarousals most likely lead to stimulation of the sympathetic nervous system and elevated blood pressure), growth aspects (obesity [as cause, including from hypothyroidism], failure to thrive/asthenia [secondary to increased energy expenditure with increased work of breathing]), precipitants of more severe OSA (intercurrent upper respiratory tract infections (URTIs) with tonsillar enlargement, exposure to cigarette smoking [doubles frequency of URTIs], allergic rhinitis).

Social history

Disease impact on child (effect on development, education, behaviour); on family (effect of snoring on other family members [if snoring in most/all members of family, presentation may be late, as thought ‘normal’], responsibility for home CPAP, financial issues; CPAP driver, private health insurance); on siblings (especially if share a room).

Past history

Age at onset, diagnosis, where and when made, investigations undertaken (e.g. formal sleep study), number of hospitalisations, treatment required (e.g. adenotonsillectomy), complications of OSA (e.g. pulmonary hypertension) or its treatment (e.g. post-adenotonsillectomy complications: nasopharyngeal stenosis, pulmonary oedema), investigation, diagnosis and treatment of underlying condition (e.g. details of craniofacial syndromes/neuromuscular disorders). Any coexistent obesity hypoventilation syndrome.

Family history

OSA, underlying inheritable diagnoses (e.g. craniofacial syndromes), atopic or allergic history, who at home smokes. Ask about any family history of sudden infant death syndrome (SIDS) or apparently life-threatening events (ALTEs), in addition to the family history of OSA, as there has been a report of OSA in infants being associated with a multiple family history of SIDS, ALTE or OSA. The family history of sleep apnoea is a risk factor for sleep apnoea in children.

Allergies

Allergic rhinitis (can contribute to/cause OSA, by nasal obstruction).

Management

Present treatment in hospital, usual treatment at home (e.g. CPAP).

Understanding of disease

By child and by parents. Ask about the degree of previous education (by doctors, by reading).

Examination

The following has been set out as a short-case approach for the lead-in of OSA, essentially as a combination of three approaches: the ‘dysmorphic child’ plus a full respiratory with an abbreviated neurological examination. If no dysmorphic features are immediately apparent, then respiratory and gait examinations usually will detect the cause, or give sufficient clues to lead to the next system. In the long case, the diagnosis will be known and so direct the examination to all findings relevant to that condition.

General impression

Note any dysmorphic facial features suggesting any of the craniofacial syndromes or other syndromes/conditions listed within the background information. Note whether there are ‘allergic facies’, with ‘allergic shiners’ (swollen discoloured eyelids; transverse nasal crease from allergic salute or ‘adenoidal facies’). Inspect the head shape, measure the head circumference (HC) (many with craniofacial syndromes, and those with some neurological disorders, will have decreased HC and abnormal skull shapes, whereas those with hydrocephalus [e.g Arnold–Chiari type II] or thicker bones [sickle cell anaemia, mucopolysaccharidoses] will have increased HC) and especially note the morphology of the eyes (microphthalmia in Hallermann–Streiff, proptosis in Crouzon and Pfeiffer, hypertelorism in Apert, Crouzon, Pfeiffer and Saethre–Chotzen, iris colobomata in CHARGE), ears (displaced and malformed in Goldenhar and Treacher Collins) and jaw. Look for midface hypoplasia (Apert, Crouzon, Pfeiffer and Saethre–Chotzen). Note any facial asymmetry (Beckwith and Goldenhar). Check size of jaw from the side (micrognathia with Robin sequence, TMJ involvement in JIA and Hallermann–Streiff). Look for any neck swelling (goitre from hypothyroidism, cystic hygroma). Check percentiles (increased weight as a cause, or decreased weight as a consequence, increased height [Marfan], decreased height [various syndromes]), Tanner staging (delayed puberty), sick or well, stridor, tachypnoea at rest, tracheal tug and use of accessory muscles. Note the skin (e.g. atopic eczema, coarse features [mucopolysaccharidoses, hypothyroidism], acanthosis nigricans [obesity]).

Respiratory and cardiovascular examinations

Examine the ears (dysmorphic with Treacher Collins and Goldenhar) and nose (inspect nasal mucosa [pale and swollen, with visible inferior turbinates, and green/clear discharge with allergic rhinitis], look for nasal polyps, then check whether both nasal airways are patent by getting child to breathe through the nose on to the cold metal of the stethoscope; there will be condensation from expired air if the nostrils are patent, if the metal is cold enough) and throat (size of tonsils, size of tongue). Note that there is no reliable relation between the size of the tonsils and the presence or degree of OSA.

Examine the chest for: asymmetry (left chest prominence with chronic increased right-ventricular activity, Beckwith–Wiedemann), deformity (Marfan), expansion, tracheal position, apex position, palpable pulmonary valve closure, right-ventricular overactivity, percussion and auscultation. Examine the cardiovascular system, noting any signs of pulmonary hypertension (single S2, P2 loud, ejection click, early diastolic murmur of pulmonary incompetence, systolic murmur of tricuspid incompetence) or cor pulmonale (signs of right-sided failure: hepatomegaly, ankle oedema).

Neurological examination

The neurological system is most quickly assessed by starting with the gait and working up, through the lower limbs, upper limbs and then the motor cranial nerves, with sensory cranial nerves last, as they are the most time-consuming and less likely to be relevant in the examination of most children with OSA.

In the long-case scenario, examine every system thoroughly. In the short case, target relevant systems. If there are dysmorphic features, then examine as per the short case in the genetics chapter. If there are coarse features suggesting a storage disease (e.g. mucopolysaccharidosis), examine the abdomen for hepatosplenomegaly. If there is hypotonia, determine whether it has a neurological cause, or a connective tissue cause; perform a neurological examination to ascertain the level of hypotonia (upper motor neurone, or lower motor neurone; if the latter, whether anterior horn cell, peripheral nerve, neuromuscular junction or muscle); perform manoeuvres to test for hypermobile joints as in Marfan syndrome (see the short case on tall stature in the Endocrinology chapter, and discussion in the long case section of the Cardiology chapter).

Management

Treatments for OSA with known efficacy include the following.

Surgical procedures

1. Adenotonsillectomy (tonsillectomy and adenoidectomy, Ts & As) remains the key treatment for OSA, and leads to significant improvement in most children with OSA, with regard to breathing, sleeping and quality of life. Reports have been somewhat contradictory as to whether there may be improvements in concentration, school performance, cognitive or developmental progress. Adenotonsillectomy has been reported as reducing the need for CPAP in morbidly obese children with OSA. Adenotonsillectomy with the addition of uvulopharyngopalatoplasty (UPPP) has been used in some units for patients with Down syndrome or cerebral palsy (CP), but other units warn against UPPP, as there is a success rate of only around 50%, and complications can include velopharyngeal incompetence.

• Adenotonsillectomy is not without some risks. There are a number of antecedent risk factors that predict requirement for paediatric ICU care postoperatively. These include: age under 2 years, craniofacial anomalies (especially midface hypoplasia and retrognathia), failure to thrive, or just thin-body habitus, hypotonia, cor pulmonale, marked obesity, previous upper airway trauma, severe OSA on PSG, concomitant UPPP and a history of prematurity. In each of these cases, as postoperative upper airway compromise is not too infrequent, here nasal mask CPAP can be useful.

• Complications of adenotonsillectomy include anaesthesia-related complications, bleeding (immediate or delayed), upper airway obstruction, nasopharygeal stenosis, pulmonary oedema, pain (local, odynophagia, otalgia), infection, nausea and vomiting, velopharyngeal insufficiency and hypersomnolence. The mortality rate is around 1 in 4000 to 1 in 27,000; morbidity is around 5–10% overall, but the morbidity rate in patients with OSA is 18–34%. Adenotonsillectomy has an overall efficacy of around 75% in improving or normalising respiratory pattern during sleep.

2. Other surgical therapies: for patients with life-threatening OSA (usually patients with craniofacial syndromes), then the following could be needed: mandibular distraction, maxillomandibular advancement, plus or minus tracheostomy (see below). Procedures to relieve nasal obstruction include inferior turbinate reduction, septoplasty, nasal valve surgery and rapid maxillary expansion. Procedures to relieve retroglossal obstruction include tongue reduction, genioglossus advancement and hyoid myotomy.

3. Tracheostomy is another surgical treatment that is available for selected patients with life-threatening OSA, particularly those with craniofacial anomalies (e.g. Pierre Robin sequence, CHARGE, Treacher Collins and Beckwith–Wiedemann syndromes), craniofacial and laryngeal tumours, or bilateral vocal cord paralysis.

Medical therapies

1. Intranasal corticosteroids are effective in decreasing OSA in children with moderate to severe adenoidal hypertrophy (associated with some decrease in adenoid size), those with allergic rhinitis, and those with residual postoperative OSA following adenotonsillectomy.

2. Leukotriene modifiers; the combination of intranasal budesonide and oral montelukast is effective in resolving mild residual OSA after adenotonsillectomy.

3. Weight loss is recommended as supplementary therapy for obsess children.

Mechanical ventilatory support

Non-invasive mask ventilatory support;for example, nasal mask continuous positive airways pressure (nasal CPAP) or nasal mask bilevel positive airway pressure (BiPAP) are both considered efficacious in paediatric OSA, but there is a high drop-out rate. CPAP provides positive pressure to the airway lumen and reduces airway collapsibility. CPAP can be titrated during PSG to ascertain optimal pressures. A snug-fitting mask is particularly important. Bilevel positive airway pressure provides a back-up rate and gives some ventilatory assistance, which is particularly useful for patients with OSA who also have sleep-related hypoventilation due to neuromuscular disease or obesity.

Long-term CPAP or BiPAP can lead to midface hypoplasia, so maxillomandibular growth has to be monitored carefully. CPAP can be indicated where Ts & As have not relieved OSA completely, or where adenotonsillectomy is not indicated or contraindicated, and before surgery in children with severe OSA.

Other therapies, which have been tried but are not used often in children, include oral appliances (such as tongue retainers and mandibular advancing devices) and supplemental oxygen therapy, which eradicates the desaturation episodes, but has no effect on the obstructive component and can worsen hypoventilation.

Short Cases

The respiratory system

This is a common case, expected to be performed well. On occasion, the patient may have a chronic rare condition such as hypoplastic lung, congenital lobar emphysema or Kartagener’s syndrome (primary ciliary dyskinesia), but more common problems include CF and CLD. Specific approaches for the latter two cases are given in the long-case section. The approaches for ‘stridor’ and for a ‘chest’ examination are described after this section.

‘Examine the respiratory system’ implies something different from ‘Examine the chest’. The former includes the hands (starting with the nails for clubbing), chest wall, praecordium, lungs, ears, nose, throat and regional lymph nodes. The latter includes chest wall (starting with this, not the hands), heart and lungs, as the primary focus of the examination, only then followed by more peripheral signs. The key is to do exactly what the examiners ask, and not interpret their instructions inappropriately.

Commence the examination of the respiratory system by introducing yourself. Note the child’s voice, which may be hoarse (e.g. in laryngotracheobronchitis). Stand back and give a general description of the child, in particular noting the growth parameters (e.g. failure to thrive with CF, BPD), nutritional status (e.g. poor fat stores in CF) and any dysmorphic features (e.g. Pierre Robin facies, with micrognathia). At this point, the child’s chest should be fully exposed, except in the case of an infant, where more subtle manoeuvring may be necessary to avoid upsetting the patient.

Note whether the child looks well or unwell, cyanosed or acyanotic, and describe any notable respiratory noises, such as stridor or wheeze, any cough and the nature of the cry in infants. Note the degree of respiratory distress (e.g. tracheal tug, intercostal, substernal and subcostal recession) and count the respiratory rate. Describe any IV lines (look at what is in the fluid being given; e.g. salbutamol, aminophylline, hydrocortisone or antibiotics), oxygen being administered (at what rate), and any nebuliser or spacer at the end of the bed.

Note any monitoring devices present, such as pulse oximetry or transcutaneous monitoring devices, and their readings. Also note any useful signs on the cot or bed. Describe any chest deformity, asymmetry, any scars and any venous access devices, and ask the child to cough. Request inspection of sputum if there is a moist, productive cough in an older child, and no sputum cup to be seen in the vicinity of the bed.

Commence the general systematic examination of the child with the hands. Then examine the head, followed by the chest, abdomen, ears, nose, palate, throat and regional lymph nodes, and the lower limbs, and request the temperature chart.

Only ask for the PEFR if it would be relevant (making sure you know the appropriate expected values for that patient). Depending on the prior findings, further examination of the fundi, skin and neurological system may be required. The various findings sought are listed in Figure 15.1, and a comprehensive listing of possible signs on initial inspection is given in Table 15.3.

Figure 15.1 The respiratory system

Table 15.3 Additional information: details of possible findings on respiratory examination

Inspection

Dysmorphic features

Nutritional status

Intervention

• Oxygen mask or catheter

• Nebuliser at end of bed

• Nasogastric tube

Monitoring devices

• Pulse oximeter

• Transcutaneous O₂ and CO₂ monitor

• Oxygen analyser in oxygen tent or head box

• Cardiorespiratory monitor

Colour Respiratory rate Respiratory noises: stridor, wheeze, cough, cry Respiratory distress, degree of

• Tracheal tug

• Sternal recession

• Intercostal, subcostal, substernal or supraclavicular retraction

Chest deformity: barrel chest, Harrison’s sulcus, pectus carinatum or excavatum, rib flaring, scoliosis, kyphosis Asymmetry (e.g. hypoplastic lung, congenital lobar emphysema) Scars (e.g. multiple intercostal drain tubes, lobectomy, associated congenital heart defects) Venous access devices (e.g. for antibiotics, in CF patients) Cough (ask patient to do this and request inspection of sputum) Upper limbs Nails: clubbing (suppurative lung disease, pulmonary fibrosis, coexistent cyanotic heart disease) Fingertips: prick marks (BSL testing in CF patients with diabetes) Palms: crease pallor (anaemia) Dorsum of hand: scars of previous multiple IVs (NICU graduate) Joints: swollen (HPOA) Pulse

• Tachycardia (hypoxia, fever, treatment with beta-2 agonists)

• Pulsus paradoxus (e.g. in severe asthma)

Asterixis: CO₂ retention Other Lower limbs

• Toenail clubbing

• Ankle oedema (right-ventricular failure)

Temperature chart Peak flow meter readings Fundi: retinal venous dilatation (CO₂ retention) Skin: eczema (e.g. with asthma) Neurological system for predisposing causes of respiratory distress, e.g. bulbar palsy (aspiration), spinal muscular atrophy (diaphragmatic breathing)

BSL = blood sugar level; CF = cystic fibrosis; HFOA = hypertrophic pulmonary osteoarthropathy; NICU = neonatal intensive care unit.

After inspection, ask the child to take a deep breath in and observe the chest expansion for asymmetry. This tends to be more useful than actually palpating during deep inspiration. Next, palpate for the apex beat, parasternal heave, palpable pulmonary valve closure and tracheal position, before percussion. Tactile fremitus can be omitted, as it is unlikely to be helpful in most children. Percussion must be performed well; have consultants check your technique while practising cases. Ensure that percussion is performed symmetrically. The apices are best percussed from behind. When percussing the axillae, it is easier with the child’s hands on his or her head. Next, auscultate in the standard manner, again symmetrically. Vocal resonance can usually be omitted. If any rhonchi are noted, it is worth asking the examiners when the last nebuliser was given.

Consultants differ in their approach to examining the chest. Some prefer to examine the anterior chest wall completely, and then the posterior aspect of the chest completely. Others prefer percussion of front and back, then auscultation in a similar manner. There is no right or wrong way to do it: the important thing is to stick to one method with which you are comfortable; do not change it on exam day.

At the completion of the physical examination, the chest X-ray (CXR) can be requested; logical and succinct interpretation is expected (see the section on reading CXRs at the end of this chapter).

The chest

With this introduction, the examiners want you to start with the chest, not the hands. After general inspection, looking for the various findings sought in a cardiac or respiratory short case, with the child’s chest fully exposed, perform a thorough examination of the lungs (as in a respiratory case) and the heart (as thoroughly as in a cardiac short case), as well as the bony structures (sternum, ribs, clavicles, spine), for findings such as scoliosis. Only when every component of the chest per se has been assessed should the systematic examination move peripherally, the direction this takes depending on the findings noted.

Stridor

This is a variation of the respiratory examination. The patients seen are usually infants, often with congenital stridor. There is a wide differential diagnosis.

After introducing yourself, stand back and give a general description of the child. Note if he or she appears well or unwell, note the growth parameters, and look for any dysmorphic/syndromal features (e.g. Opitz syndrome, with hypertelorism, cleft lips, protruding ears and laryngeal cleft), or the features of the ‘ex-premmie’ NICU graduate (prolonged intubation, resultant subglottic stenosis). Scan the child for any evidence of capillary haemangiomata, particularly in the ‘beard’ distribution of the face and neck (associated subglottic haemangioma).

Note the infant’s colour, posture (e.g. hyperextended neck with supralaryngeal problems, hypertonic spastic posturing in infants with cerebral palsy and pseudobulbar palsy), activity (paucity of movement with some neurological causes) and the degree of respiratory distress. Note the respiratory rate, tracheal tug and degree of chest recession (sternal, intercostal, substernal, subcostal or supraclavicular). Also note the following:

1. Whether the child is receiving any supports, such as nasogastric feeding (which implies at least one patent choanal opening), intravenous fluids, oxygen.

2. Whether the child has been receiving supports (which are temporarily unnecessary), such as nebulised therapy or an oropharyngeal airway on the bedside cupboard, or whether there is perinasal linear skin reddening, suggesting recent removal of tape securing a nasogastric tube.

3. Whether the child is being monitored; for example, with pulse oximetry.

Observe whether the child is a nose or mouth breather (mouth breathing inferring nasal obstruction; e.g. due to choanal stenosis), and if there is any drooling (suggesting supralaryngeal obstruction) or pooling of secretions (neurological causes).

Listen to the child’s breathing to determine in which phase of respiration the noise occurs. Note that fixed obstructive lesions causing significant cross-sectional area reduction of the airway (anywhere) can cause inspiratory and expiratory (biphasic) stridor, irrespective of whether the lesion is extrathoracic (above the clavicles) or intrathoracic (below the clavicles). Purely inspiratory stridor suggests a non-fixed obstruction, usually above the clavicles/extrathoracic, such as a laryngeal or supralaryngeal obstruction. Inspiratory and expiratory (biphasic) stridor may infer a non-fixed lesion with tracheal involvement. Expiratory noises alone are more likely non-fixed and below the clavicles (tracheal). Laryngeal problems may change the character of the voice (e.g. a hoarse voice with unilateral vocal cord paralysis, or with laryngitis) or the cry (e.g. weak with vocal cord problems; note that bilateral vocal cord palsy is more often associated with a normal cry and normal voice). Crying itself worsens the stridor in laryngomalacia or subglottic haemangioma. Note the relative timing of inspiration and expiration: in laryngeal disorders, inspiration is prolonged; while in bronchial obstruction, expiration is prolonged.

If the mother changes the infant’s position when the child is distressed, note any change in the stridor with the crying and with the repositioning.

The child’s head posturing must be noted, as it may give a clue to the level of the problem. Laryngeal or supralaryngeal narrowing tends to make a child hyperextend the neck (classic example: epiglottitis) to increase the upper airway diameter.

Inspect the nose, noting whether it permits passage of a nasogastric tube and whether there is any movement of mucus with respiration, inferring patent nostrils. Inspect the mouth for any scars from repaired cleft lip, glossoptosis or micrognathia (syndromal diagnoses) and, when the child opens the mouth, note any obvious cleft palate. Inspect the neck for any asymmetry (e.g. lymphatic malformation [‘cystic hygroma’], neoplasm). Inspect the chest for scars (e.g. previous tracheostomy, previous multiple intercostal drain tubes in the NICU graduate), deformity (e.g. pectus excavatum, Harrison’s sulci), increased anteroposterior diameter (e.g. in coexistent CLD in the NICU graduate) and degree of chest recession.

Before the child is too distressed, if you suspect nasal obstruction, the ‘metal condensation test’ can be performed in a few seconds. Simply hold the metal arm of your stethoscope under the infant’s nostrils, and as the metal is (usually) cold, any nasal breathing will result in moisture condensing on the metal, confirming nostril and choanal patency.

Some aspects of the examination of the mouth are unpleasant and are best deferred until the end of the examination, but must not be omitted (see below).

Palpate the neck for any masses (e.g. lymphatic malformation [cystic hygroma]). If any masses are present, examine these in the standard manner for any lump (i.e. size, shape, consistency, pulsatility, attachments, fluctuation, transillumination, auscultation, regional lymph nodes). At this stage, if there is a neck mass, turn the child’s head to either side, then flex and extend the neck to assess if this worsens or alleviates the stridor.

Palpate the trachea to detect any deviation. Also palpate the apex beat (deviation), any parasternal heave or palpable pulmonary valve closure (pulmonary hypertension and cor pulmonale), and then percuss across the upper chest to detect any retrosternal mass compressing the airway. Auscultate the lungs (to confirm the timing of the stridor, and detect associated respiratory disease; e.g. CLD) and the heart, for loud second sound and any evidence of right-heart failure or coexistent heart disease (as in some syndromal diagnoses). Now, with auscultation completed, move the infant into a supine and then a prone position, to detect any change in the stridor: in laryngomalacia, the stridor diminishes when prone.

At this point, it may be worthwhile looking carefully at the skin for any ‘strawberry’ haemangiomata that may have passed unnoticed.

Now come the least pleasant aspects of the examination:

1. Inspect the oral cavity, using a spatula and torch, looking for cleft palate and any obvious swellings or tumours (e.g. retropharyngeal or tonsillar).

2. Test the gag reflex and the suck (for bulbar dysfunction in neurological causes).

3. Palpate the tongue all the way back, to detect any mucus retention, cyst or other obstructive lesion.

4. If the condensation test suggests complete obstruction, it is now time to request a feeding tube and pass this down each nostril. Only do this at the very end of the examination, as it always upsets the child.

If a syndrome seems likely, look for other dysmorphic features.

If there is a suggestion of a neurological aetiology, perform a gross-motor assessment, followed by testing the long tracts, and then the motor cranial nerves (starting from cranial nerve XII and progressing upwards to III).

Always request the temperature chart at the completion of your examination (e.g. for retropharyngeal abscess).

Give a brief, logical differential diagnosis, and after this request a posteroanterior (P-A) chest X-ray (CXR) and a lateral airways film.

Chest X-rays

Accurate interpretation is expected. Note the date of the X-ray and the name, to check that it is the correct film. Then note which side is labelled ‘right’ to avoid missing dextrocardia (although it should have been noted clinically), particularly in the child with clubbing and purulent sputum, who has Kartagener’s syndrome (immotile cilia/primary ciliary dyskinesia) and not CF. Note whether the film is well centred. This is the time to quickly scan the bony structures, as rotated films will show asymmetry of clavicles on the P-A view. Check the chest symmetry and note any scoliosis or rib crowding. Check that the film is well penetrated, and has been taken during a full inspiration. Expiratory films are notoriously difficult to interpret and may be quite misleading. Note the centring of the trachea and the cardiac shadow, checking for any deviation. Assess the cardiac size: the cardiac diameter is normally 50% or less of the cardiothoracic diameter (except in neonates, where it can be 60%) (see Figure 15.2). The heart may be enlarged due to pathology related to the lungs, such as cor pulmonale. The cardiac contour is then inspected, looking for evidence of the following:

1. Loss of right-heart border definition, which indicates right middle-lobe involvement.

2. Loss of apex definition, which indicates lingula involvement.

3. Increased opacification behind the heart, usually in a ‘sail’ or triangular shape, indicating left lower-lobe involvement.

4. A prominent pulmonary artery shadow, which can indicate pulmonary hypertension (PHT) .

5. A prominent right-atrial shadow, which can occur with PHT.

6. A prominent right-ventricular region, which can occur with PHT. (See Figure 15.3.)

Figure 15.2 Chest roentgenography.

Diagram showing how to measure the cardiothoracic (CT) ratio from the posteroanterior view of a chest X-ray film. The CT ratio is obtained by dividing the largest horizontal diameter of the heart (A B) by the longest internal diameter of the chest (C). Myung Park 2007. Pediatric Cardiology for Practitioners, 5th edition, p. 66, Figure 4.1.

Figure 15.3 Posteroanterior and lateral projections of a normal cardiac silhouette.

Note that in the lateral projection, the right ventricle (RV) is contiguous with the lower third of the sternum and that the left ventricle (LV) normally crosses the posterior margin of the inferior vena cava (IVC) above the diaphragm. AO, aorta; LA, left atrium; LAA, left atrial appendage; LPA, left pulmonary artery; PA, pulmonary artery; RA, right atrium; RPA, right pulmonary artery; SVC, superior vena cava. Redrawn from; Myung Park 2007. Pediatric cardiology for practitioners, 5th edition, p. 66, Figure 4.2.

Focus on the lung fields. Note any asymmetry in the lucency of the lungs (e.g. in congenital lobar emphysema), any hyperinflation (as in asthma, with ‘flattened’ diaphragm shadows and increased lucency). Focus on the diaphragm shadows, looking for the following:

1. Loss of the line of the left hemidiaphragm suggests left lower-lobe involvement.

2. Loss of the line of the right hemidiaphragm suggests right lower-lobe involvement.

3. Loss of a clear costophrenic angle suggests pleural effusion (remember to examine the apices for a pleural cap).

4. The right hemidiaphragm is normally higher than the left, due to the liver; if the lungs are hyperinflated, the hemidiaphragms may be at almost the same level.

Note any focal areas of increased opacification, and any generalised increase in opacification in perihilar or peripheral areas. If it is unclear on assessing the P-A film which region of the lung is involved (as is particularly the case in consolidation affecting the ‘midzone’ of the lung fields), request a lateral film.

In assessing the lateral film, first note the bony structures. Note the degree of opacification of the vertebrae: normally the upper vertebrae are quite opaque, due to the overlying shoulder region, and as one progresses down the spine, the vertebral bodies appear increasingly lucent, because of the lack of overlying soft tissues in that region. Thus, if there is increased opacification of the lower vertebral area, there may be consolidation, or other process, involving the posterior segments of the affected lobe. Also note any kyphosis (rare) or rib abnormalities. Check the tracheal position followed by assessing the positions of the hemidiaphragms. Now inspect the lung fields; they are normally obscured in the postero-superior aspect (by the shoulders) and in the anteroinferior aspect (by the heart). Look for the interlobar fissures, which may delineate a collapsed or consolidated area.