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Respiratory symptoms in the oncology patient

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Fever with Respiratory Tract symptoms

Shared care information

Children on treatment are susceptible to both common respiratory pathogens presenting atypically and to uncommon pathogens that infect immunocompromised patients. Any respiratory infection should be discussed with the paediatric oncologist on call - during working hours if the patient appears well or immediately if they are unwell or have an oxygen requirement.

Children who develop progressive respiratory compromise for whatever reason should be discussed with the paediatric oncologist on call regarding the need for transfer prior to further investigations.

The recommended approach is predicated on a basic consideration of whether the child has respiratory symptoms in association with febrile neutropenia, or not.

Please refer to the flow chart below for investigation of the patient presumed to have an infective cause for their respiratory symptoms.

Respiratory flow chart

Investigations

Neutropenic children may have minimal or no radiological changes so:

  • a normal CXR does not exclude significant infection
  • CT chest should be considered in patients with prolonged neutropenia, prolonged symptoms or failure to respond to empiric antibiotic treatment

Microbiology testing

It is important to be aware of what your microbiology department tests for when ordering investigations such as respiratory virus screens, and to discuss the use of extended panels with ID in patients with ongoing symptoms where microbiological investigations have been negative.

Table 1: Tests available at the NZ centres providing Paediatric Haematology/Oncology services

Respiratory table 1

Bronchoscopy and lavage, and non-bronchoscopic bronchoalveolar lavage

Bronchoalveolar lavage (BAL) or non bronchoscopic bronchoalveolar lavage (NBBAL) should be considered if the differential diagnosis includes a diagnosis that may not be readily identified from the routine tests recommended for febrile neutropenia with respiratory symptoms.

Bronchoalveolar lavage (BAL) should be considered early as it may be dangerous in the face of increasing respiratory failure. Arrange with respiratory team, paediatric surgeon/radiologist, paediatric anaesthetist and microbiologist. Consult with ICU if danger of severe respiratory compromise following BAL (unlikely to occur if FiO2 < 0.3).

It is imperative to discuss the case with the microbiologist/ID physician prior to BAL or biopsy who will have knowledge of current viral infections in the community and guide further tests.

Wherever possible, BAL or NBBAL should be performed as soon as possible in order to maximise the likelihood of identifying an organism. BAL done within 24 hours of starting antibiotics has a 55% yield, whereas in those done after 24 hours the yield is 30%1. Likewise, even after 24 hours, the sooner BAL/NBBAL is done, the greater the likelihood of finding an organism (<3d: 65%, 3-14d: 55%; >14d: 35%)2.

Investigation of BAL/NBBAL samples should include:

  • Microbiology: M,C&S; fungal culture; AFB's
  • Virology: PCR for ACH Resp viruses Panel
  • Atypical pneumonia panel
  • Sample for cytology for underlying disease
  • Biochemistry: galactomannan
  • Other tests: It is suggested these are discussed the Paediatric Respiratory specialist(s) who support the relevant Paediatric Oncology service.

Lung Biopsy

Lung biopsy is indicated if there is ongoing concern about an infective cause of respiratory symptoms, but prior investigation has been negative. It may also be indicated if there is concern the differential diagnosis includes a non-infective respiratory disorder.

Biopsy should be considered early as it may be dangerous in the face of increasing respiratory failure. Whether to do a lung biopsy, and the type of biopsy, is dependent on the position of the lesion and the availability of surgeons or interventional radiologists.

If lung biopsy is contemplated, this should be discussed with the Starship or Christchurch Paediatric paediatric respiratory consultant and the pathology service where the biopsy will be performed. It is possible that samples may need to go to an overseas centre for a second opinion by specialist in Paediatric Pulmonary Pathology.

Management

  • Commence high-dose IV cotrimoxazole (Trimethoprim component of cotrimoxazole dose 5 mg/kg/dose 6 hourly IV) and erythromycin as soon as BAL/biopsy performed
  • Consider empirical antifungal therapy
  • Direct further treatment according to the organism isolated e.g., Ganciclovir for CMV, ribavirin for RSV, oseltamivir for influenza.
  • Several small studies suggest that severe adenovirus infection may benefit from treatment with combined cidofovir and IVIg but there are no randomised controlled trials
  • There is no good evidence for antiviral therapies for treatment of parainfluenza
  • Human metapneumovirus has recently been identified as a cause of idiopathic pneumonia after SCT. This virus is the second commonest cause of bronchiolitis in immunocompetent children. At this time there is limited data on treatment options though nebulised and IV ribavirin have been used in the lung transplant setting
  • Polymicrobial infections of the lung are not uncommon e.g., pneumocystis and CMV
  • Consider drug toxicity e.g., methotrexate, bleomycin

Interstitial Pneumonitis

Causes include:

Viral parainfluenza, adenovirus, RSV, human metapneumovirus, influenza, VZV (usually preceding rash), CMV, measles (usually no preceding rash) 
Bacteria  Mycoplasma, Legionella, Pertussis 
Parasites and fungi  PCP, Candida, aspergillus 

Investigations

  • Sputum/cough swab M,C+S for bacteria, fungi in older children
  • Immunofluorescence or PCR of NPA/sputum, influenza, parainfluenza, adenovirus, RSV, herpes simplex, CMV, human metapneumovirus
  • Pneumocystis stain and culture
  • Urinary PCR for CMV and Legionella
  • Legionella antigen
  • CT chest
  • Broncho-alveolar lavage and/or biopsy - CT guided, thoracoscopic or open

Respiratory infections without Pneumonitis

Investigations

  • sputum for M,C+S in older children
  • nasopharyngeal aspirate or deep nasopharyngeal swab for respiratory viruses immunofluorescence or PCR
  • Mycoplasma IgM
  • Legionella antigen on urine
  • CXR, and if normal, consider CT chest

Management

  • Empirical antibiotic cover as for common childhood respiratory infections
  • Patients with significant hypoxia should start empiric high dose cotrimoxazole for PCP and have BAL performed

Mycoplasma pneumoniae

Mycoplasma is a frequent cause of pneumonia, including sometimes an interstitial picture, in children with ALL in remission

Clinical features

  • Cough
  • Fever
  • It may be indolent with a chronic non-progressive course and recur following cessation of treatment with erythromycin

Investigations

  • sputum for M,C+S in older children
  • nasopharyngeal aspirate or deep nasopharyngeal swab for respiratory viruses immunofluorescence or PCR
  • Mycoplasma IgM
  • Legionella antigen on urine
  • CXR, and if normal, consider CT chest

Management

  • Roxithromycin 4 mg/kg/dose PO bd, or
  • Erythromycin 7.5 mg/kg/dose IV or PO q12h
  • Macrolides inhibit cytochrome P450 enzymes so there are interactions with CSA, vincristine, etc. There are fewer problems with clarithromycin, however this is not subsidised

Bordatella Pertussis (Whooping Cough)

Current low immunisation rates in New Zealand, coupled with the relatively low immunogenicity of the vaccine, means that outbreaks of pertussis are occuring.

Clinical features

  • Chronic cough - may be classical coughing fit followed by inspiratory whoop, or a persistent nagging cough
  • Ask about relatives/contacts with similar symptoms

Investigations

  • Nasopharyngeal swab for culture and PCR

Management

  • Erythromycin 12.5 mg/kg Q6hr PO for 14 days, or Roxithromycin 4 mg/kg BD PO
  • Contact infection control for contact tracing
  • Keep in respiratory isolation if admission is required

Prevention

Patients should receive prophylactic erythromycin for 10 days following confirmed contact. Macrolides inhibit cytochrome P450 enzymes so there are interactions with CSA, vincristine, etc. There is less problem with clarithromycin compared with erythromycin, although this is not funded for use in these circumstances.

Viruses

See information on viruses (influenza) with respiratory involvement under Viruses

Pneumocystis Jirovecii (carinii) Pneumonia (PCP)

See separate index entry for PCP

Non-infective causes of respiratory symptoms

These can be conveniently grouped by the timing of their appearance in the course of the malignancy.

respiratory diagram 2

References

  1. Yacoub. Mediterr J Haematol Infect Dis. 2015.

  2. Kotiman. Thorax. 2010

  3. Williams KM et al. A clinical algorithm identifies high risk pediatric oncology and bone marrow transplant patients likely to benefit from treatment of adenoviral infection. J Ped Hem Oncol; 2009; 31(11):825-31.

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Document Control

  • Date last published: 15 August 2016
  • Document type: Clinical Guideline
  • Services responsible: National Child Cancer Network, Paediatric Respiratory
  • Author(s): Scott Macfarlane, Julian Vyas, Siobhan Cross
  • Owner: Scott Macfarlane
  • Review frequency: 2 years