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Non-infective respiratory complications in Cystic Fibrosis

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See also Investigation of Respiratory Physiology in Cystic Fibrosis.

In This Document

Haemoptysis
Wheezing
Pneumothorax
Pulmonary Hypertension
Atelectasis
Respiratory Failure 

Haemoptysis

It is not unusual in cystic fibrosis or bronchiectasis to have small volumes of haemoptysis, usually old blood, mixed in with sputum. It is thought to arise from chronic inflammation in the area of a small bronchial artery, and  is considered indicative of bacterial exacerbation. First line treatment is antibiotics.

Haemoptysis in cystic fibrosis is unlikely to cause any significant haemodynamic problems. The child usually produces small amounts which settle quickly with treatment. It is reportedly rare (but not impossible) in children under the age of 10, or with FEV1 > 75%2.

Indicators (red flags) of more significant haemoptysis can include:

The patient may complain of a gurgling sensation, which is reported to be an accurate localising sign for the site of bleeding. There may be marked anxiety if they have already coughed up blood ("a little blood goes a long way").

The differential diagnoses include:

It is important to consider non-cystic fibrosis related causes as well e.g. pulmonary embolism after immobility or intercontinental flight, use of oral contraceptive pill (in older teenagers). It is also important to consider if the bleeding might originate from oesophageal varices, rather than from the airways. In non-cystic fibrosis patients, invasive Aspergillus fumigatus lung disease is a well recognised cause of major haemoptysis. However it is not thought to be a common causal agent in cystic fibrosis. The reasons for this remain unclear. Bacterial infection is thought to promote risk of haemoptysis due to the vascular changes associated with chronic infection, and especially Vascular Endothelial Growth Factor (VEGF) production13.

Investigation and Management

Blood Volume
  small (streaks/ mixed in with sputum only) medium (Frank blood  < 250 mls/d) large (> 250 mls/d or >100mls/d over several days)
Investigations O2 saturations
Full blood count, platelets, coagulation
Group and hold
Sputum MC&S
O2 saturations
Full blood count, platelets, coagulation
Cross match
Sputum MC&S
Chest xray
Consider CT angiography and/or rigid bronchoscopy
 O2 saturations
Full blood count, platelets, coagulation
Cross match
Sputum MC&S
Chest xray
Consider CT angiography and/or rigid bronchoscopy
Treatment Stop physiotherapy for 48 hrs
Stop dornase for 48 hrs
Stop NSAIDs
Oral antibiotics
Consider Vitamin K if INR elevated
Stop physiotherapy for 48 hrs
Stop dornase for 48 hrs
Stop NSAIDs
IV antibiotics
Transexamic acid
Discuss with centre providing bronchoscopy re: query embolisation if persists/clinical deterioration.
Consider Vitamin K
Stop physiotherapy for 48 hrs
Stop dornase for 48 hrs
Stop NSAIDs
IV antibiotics
Transexamic acid
Transfer to centre providing bronchoscopy re: embolisation or query lobar resection
Consider Vitamin K

Notes:

  1. If there is a possibility that the child may need embolisation and/or surgical intervention, which is not available locally, it is better to refer to a centre which can provide this sooner, even if they are not ultimately used.
  2. Embolisation is best performed using gel foam, as placement of coils can sometimes hamper future catheterisation of the same arterial branch if haemoptysis from the same area persists.
  3. In life threatening haemoptysis, the child must be ventilated as a matter of urgency. Discuss specific ventilation strategies with PICU, but generally a high positive end expiratory pressure (PEEP) is indicated.

Wheezing

Recurrent wheeze is very common in cystic fibrosis. Skin Prick Testing or Specific IgE testing to aero-allergens other than to Aspergillus fumigatus is generally not indicated or helpful. Treatment of wheeze should be along the lines of conventional asthma treatment (bronchodilators as required, inhaled corticosteroids (ICS). ICS/long acting beta agonist (LABA) combination).

A small group of children with cystic fibrosis can have troublesome wheeze, characterised by:

In these children, it is important to consider co-existence of gastro-oesophageal reflux disease (GORD), allergic bronchopulmonary aspergillosis (ABPA), atelectasis/ mucus impaction, or even a new organism.

If routine investigation for the above differential diagnoses does not reveal a cause, then the child should be considered for a flexible bronchoscopy and lavage. If this procedure cannot be supported by an appropriately experienced bronchoscopy service locally, then the need for bronchoscopy and likely timing should be discussed with the Starship Cystic Fibrosis team.

Pneumothorax

A recent summary of pneumothorax in cystic fibrosis has suggested an annual incidence of 0.64%, and a cumulative frequency of 10 years of 3.4%4. Pneumothorax in cystic fibrosis is a concern; and recurrent or refractory air leak is listed as an indication for lung transplant. The Royal Brompton Hospital guidelines recommend that "all but the most trivial pneumothorax in a stable patient mandates admission to hospital." Risk factors for an air leak in include FEV1 <30% predicted, P aeruginosa, B cepacia, Asp Fumigatus, enteral feeding, previous massive haemoptysis.

Consider a pneumothorax if a child with cystic fibrosis presents with unexpected deterioration, unexpected chest pain, or worsening breathlessness. Pneumothorax may not present with the typical clinical signs as for non-cystic fibrosis patients. The reduced elasticity of the cystic fibrosis lung means collapse of the ipsilateral lung may not occur, and there may not be marked mediastinal shift. However tension within the pleural space can still compromise venous return. Given the likelihood of the cystic fibrosis lung not collapsing, diagnosis can sometimes be difficult on plain chest X-ray. If clinical concern persists despite an innocuous looking chest X-ray, HRCT is indicated.

A non-tension pneumothorax of >20% will likely need intercostal drain insertion, but a smaller one may be managed conservatively.

A chest drain may be sufficient to allow the lung to heal, and resolve the pleural collection of air. However, with persistent air leak, or if lung compliance does not encourage re-expansion, other strategies may be necessary. These may include use of negative pressure suction on the drain, chemical pleurodesis, or pleurodesis via video-assisted thoracoscopic surgery (VATS). Changes in surgical techniques for lung transplant have meant that previous pleurodesis is no longer a contraindication for lung transplant. General guidance on pneumothorax is not published in Australasia. The British Thoracic Society Guidelines on Pleural Disease (2010) includes a section on spontaneous pneumothorax and should be consulted for any more specfic queries on management5.

Pneumothorax in a child who is already receiving non-invasive ventilation (NIV) adds significant complication to the overall management of the child. If this clinical combination arises, each case should be assessed on their individual merits as to whether to stop or continue with the nocturnal support. It is suggested that in such instances the child's acute problem should be discussed with the paediatrician overseeing the NIV, as well as a Respiratory Paediatrician with expertise in cystic fibrosis.

After suffering a pneumothorax, the child may need to avoid pressurised air flight for a period of time. Recommended intervals between pneumothorax and flying have generally become less stringent over time. Before advising a whanau/family on what is current best practise, the most up to date version of BTS or ATS guidance should be consulted6. Current guidance is that the patient can fly 7 days after an air leak has been demonstrated to have resolved radiologically. It is important to inform the patient and whanau/family that for adults with pre-existing chronic lung disease, there is a high risk of recurrent pneumothorax during the following year after the initial leak. There are no data for children with cystic fibrosis.

Pulmonary Hypertension

Pulmonary hypertension in cystic fibrosis is generally associated with end stage lung disease. It is highly unlikely to be encountered in a paediatric context. On the rare occasion when a child or teenager reaches a palliative stage to their clinical course, pulmonary hypertension may have clinical relevance.

Pulmonary hypertension can arise from lung disease (Class 3, WHO classification). Review of adult studies suggest that in cystic fibrosis, pulmonary hypertension is strongly correlated with chronic alveolar hypoxia. Tonelli proposes a paradigm of lung pathophysiology to explain the development8. In addition, obstructive sleep apnoea from nasal polyps, and the association between portal hypertension and pulmonary hypertension may also be relevant in the development of pulmonary hypertension in cystic fibrosis.

Atelectasis

The inherent viscosity of the mucus in cystic fibrosis makes atelectasis an essential component of the development of bronchiectasis in cystic fibrosis.

From time to time, a more acute episode of atelectasis may occur, which causes increase in symptoms, and/or radiological change. It is not possible to predict whether such an area will clear just with ongoing adherence to the routine therapies already in use (twice daily physio, current use of mucolytics, exercise), or whether an increase in therapy is needed. It is also not clear the extent to which anatomical location and duration of an acute atelectasis will affect longer term lung morbidity.

Just as prognosis is uncertain, so is the optimal approach to escalating treatment. The suggested algorithm below is based on clinical experience only.

Flexible Bronchoscopy for significant atelectasis

Flexible bronchoscopy should be performed after other less invasive manoeuvres to resolve the atelectasis have been unsuccessful. Flexible bronchoscopy will allow assessment of other co-mordibities which may be influencing the refractory nature of the atelectasis. Recognised airway co-morbidities in cystic fibrosis include malacia (which might be more prevalent in cystic fibrosis) and casts from allergic bronchopulmonary aspergillosis (ABPA). Coincidental possible co-morbidities include anatomical variation eg aberrant airway branching morphology, compression from previously unrecognised aberrant course to mediastinal vessels, compression from previously unrecognised congenital cardiac disease, lymph node enlargement, unrecognised foreign body etc.

Dornase alpha may be instilled into the lower respiratory tract at the time of flexible bronchoscopy. There is no standardised dose, but at Starship Children's Hospital the maximal dose is 5mg (5 mls) dornase alpha made up to a total of 10mls with 0.9% saline.

If a child is more acutely unwell as a result of the atelectasis, it may be necessary to consider flexible bronchoscopy at an earlier stage. Wherever possible, discussion with the clinical service which will receive the request for bronchoscopy should be initiated before a flexible scope is urgently required.

Respiratory Failure

Chronic respiratory failure in cystic fibrosis is discussed in Sleep and Sleep disordered breathing in Cystic Fibrosis.

Acute respiratory failure

Respiratory failure, i.e. hypoxia with or without hypercapnia, is usually a sign of severe lung disease in cystic fibrosis and associated with high mortality. The cause of the respiratory failure may influence the likelihood of survival from the acute event. In Texereau J et al. Respir Res. 2006;7:14, out of 22 adult patients with acute respiratory failure from haemoptysis or pneumothorax, almost 60% survived to discharge. In contrast 4 of 12 patients who had acute respiratory failure due to infective exacerbation survived. Even for those who survived an acute episode of respiratory failure, the outlook was poor, with a median survival post-discharge of approximately 15 months. An earlier paper12 described 20 children with cystic fibrosis admitted to PICU, of whom 9 survived. Both studies identified pre-morbid factors associated with a poor outcome: low BMI22,23, poor bone mineral status22, and FEV1 <25% predicted23. The Texerau study observed use of non-invasive ventilation (NIV) for acute respiratory failure was associated with better longer term survival. Similarly, Vedam12 speculated that longer term positive outcomes for 5 of the survivors might have been associated with long term NIV support after discharge from the PICU.

Admission patterns to ICU for adults and children with cystic fibrosis are different. UK data13 showed that only 8% of adults died in an ICU. In contrast, a separate paediatric study14 suggested almost all deaths in children with cystic fibrosis occur in hospital, and approximately half occurred on a PICU.

Suggested approach to acute respiratory failure

If acute respiratory failure occurs ion the context of an inexorable decline from cystic fibrosis, and where a plan for palliative care has previously been agreed, then discuss with parents (and the child where appropriate) whether escalation of treatment is truly in the patient's best interests. This will require explanation of what intensive treatment will involve for the child (sedation, vascular access etc), and where it can be provided (i.e. how far from the home area). In addition, it should be stressed that despite the whanau/family (and patient) wishes, the receiving intensive care unit may decline to accept the patient if death seems inevitable, even with a period of intensive care support.

In some instances admission to a paediatric intensive care unit (PICU) for acute non-invasive support may be indicated. This should be discussed with the receiving PICU to establish if they feel this is an appropriate step to take. Non-invasive ventilation may be precluded by a need for airway protection (i.e. intubation) for transport.

Lung transplant can be a topic for discussion by whanau/families at this point. Ideally, this option would have been thoroughly explored before the child has reached the point of acute respiratory failure. As a general rule in New Zealand, referral for transplant assessment at the point of acute respiratory failure is not appropriate for several reasons. Transplant survival outcomes are exceedingly poor for those who are in acute respiratory failure prior to undergoing the procedure. There can often be superadded infection, which increases risk once the patient is immunosuppressed. Extra-pulmonary organ injury from the acute respiratory failure also increases the risk of non-pulmonary complications post transplant. Notwithstanding the outcome caveats about sub-optimal survival, average waiting times for donor organs in New Zealand are usually of the order of several months, but with no guarantee of a match being found at any time. To ventilate a patient with an ultimately fatal chronic condition for a potentially indeterminate length of time is considered unethical.

Colleagues caring for a child with acute respiratory failure are encouraged to discuss the case with centres with PICU support, and also the cystic fibrosis team at that centre.

Given that clinical decisions about non-escalation of treatment in cystic fibrosis are relatively uncommon for any individual practitioner, and can be inherently difficult, colleagues are encouraged to discuss any issues around this with other members of the cystic fibrosis network.

 

References

  1. British Thoracic Society. Managing passengers with respiratory disease planning air travel http://www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/Air%20Travel/Guidelines/FlightRevision04.pdf 
  2. Barben JU et al. J Cyst Fibrosis, 2003; 2: 105
  3. Flume P. Respir Care. 2009; 54: 618-627
  4. Kioumis IP et al. J Thorac Dis. 2014; 6: S480-S487. doi: 10.3978/j.issn.2072-1439.2014.09.27
  5. MacDuff A, Arnold A, Harvey J. Thorax. 2010;65: S18. doi:10.1136/thx.2010.136986
  6. Nicholson TT, Sznajder JI. Annals ATS. 2014;11:1614. doi: 10.1513/AnnalsATS.201406-234PS
  7. Lippert HL, Lund O, Blegvad S, Larsen HV. Eur Respir J 1991;4:324-331
  8. Tonelli AR. Curr Opin Pulm Med 2013;19:652. doi: 10.1097/MCP.0b013e3283659e9f
  9. Flight WG, Hildage J, Webb AK. J R Soc Med 2012;105:S44. doi 10.1258/jrsm.2012.12s009
  10. Wyatt CA, Burns L, Wood RE. Am J Respir Crit Care Med . 2013; 187:A1173. doi: 10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A1173
  11. Texereau J et al. Respir Res. 2006;7:14
  12. Vedam H et al. J Cyst Fibrosis. 2004;3:8. doi:10.1016/j.jcf.2003.12.003
  13. Jones A, Bilton D, Evans TW, Finney SJ. Respirology. 2013;18:630
  14. Urquhart DS et al. Arch Dis Child. 2013;98:123

Document last updated: April 2017

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