Breathing difficulties are frequent in children with cancer, and represent an important cause of admission to the pediatric intensive care unit (PICU) in patients of this kind.1–5 Such breathing difficulties may appear both at the time of diagnosis of the neoplastic disease—in some cases constituting its only symptom—or as a consequence of the treatment provided, or of the course and complications of the illness.2,3,6

The underlying etiology is varied and requires adequate and early treatment.4 The present review describes the most common forms of breathing difficulties in children with cancer, offering a description of their clinical manifestations, diagnosis and initial treatment. The study is divided into three parts: oncological emergencies, infections and complications of treatment (iatrogenesis). We have not included breathing difficulties in bone marrow transplant patients in this article, since in view of their specific characteristics, these will be dealt with in a separate review.

Oncological emergencies are all those acute breathing difficulty conditions derived from the existence of cancer.2–4,7 Such problems may appear both at the onset of the disease and during its subsequent course. In all cases the clinical manifestations are the basis for suspecting the diagnosis, and the main aim of management is always to secure the airway of the patient.8,9

Oncological treatment gives rise to partial or complete patient immune suppression.25 This in turn facilitates and increases the development of infections, particularly in neutropenic children (<500 total neutrophils/μl of peripheral blood2).

Respiratory infections in children with cancer are of a varied and complex etiology,26 and give rise to important morbidity–mortality27,28 (up to 80% of the cases with associated clinical manifestations of sepsis2,29). Due to the prolonged hospital stays and poor background immune condition of these patients, nosocomial pathogens are frequent causal agents.27,28 In practical terms, we can distinguish two groups of patients according to their degree of immune suppression (Table 1):

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  Patients in the early phases of treatment or with over 500 total neutrophils: suspicion should focus on gramnegative30 (colonization of the airway by bacteria present in the digestive tract) and grampositive pathogens (generally staphylococci or streptococci), present in the skin, and which cause infection through central venous catheters.9,31

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  Patients with prolonged neutropenia or severe immune suppression (under 100 total neutrophils, or undetectable counts): we add fundamentally opportunistic agents,30 such as fungal (Candida as the most common species, and Aspergillus as an example of fungal infection with important mortality and complications32–34) and viral infections (herpes simplex virus or adenovirus). In all these cases, early and adequate empirical treatment should be started.9,28

As a result of the existing immune suppression, few manifestations of inflammation are observed (with no important leukocytosis or increases in acute phase reactants)—the only signs and symptoms being discrete dyspnea, cough or mild chest discomfort.2,35,36

Chest X-rays are useful only for evolutive monitorization of the disease, since there may be no initial changes because of the incapacity to generate consolidations and leukocyte infiltrates.28,32 If such changes do appear, their distribution may be useful for establishing a tentative diagnosis (Table 2).2,37 Thoracic CT is the instrument of choice for establishing an early diagnosis, since it is able to identify alterations even in the presence of normal plain X-ray findings.2,28,32

Adequate support of the clinical condition of the patient is required, with the optimization of oxygenation. Respiratory wellbeing is to be sought, reducing the existing dyspnea as far as possible (mask with a reservoir or noninvasive positive pressure ventilation).2,3,35,38 When mechanical ventilation is required, specific ventilation maneuvers are usually needed, with high oxygen output, high pressure peaks, and peak end expiratory pressure (PEEP) values higher than those usually employed (between 6 and 10cm H2O).

Associated early empirical treatment is essential, combining antibiotics, antifungal agents and antiviral drugs.39 The most commonly used drugs are specified below (Table 3):

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  Antibiotics: broad spectrum betalactams are indicated, such as cefepime, meropenem or imipenem39,40 combined in the case of suspected grampositive infection with a glycopeptide (vancomycin).27,31,35,41 In the case of important hypoxemia without major radiological alterations, treatment with trimethoprim sulfamethoxazole should be considered, due to possible infection with Pneumocystis jirovecii.42

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  Antifungals: a common first choice is fluconazole (generally used as prevention against fungal disease, and not useful in the case of Aspergillus infection), which should be replaced by amphotericin B (liposomal or lipidic), micafungin or voriconazole when suspecting infection by a fungus other than Candida, or in the case of a poor patient response to the initial empirical treatment provided.27,32,36

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  Antivirals: these drugs are indicated in the case of great immune suppression or when viral infection is suspected. Ribavirin is indicated in the case of respiratory syncytial virus (RSV) infection,43 and empirical treatment with oseltamivir is advised in the presence of influenza or pseudoinfluenza symptoms. It is also common to use ganciclovir or aciclovir in the case of possible pneumonia due to herpes simplex virus.27,32,36

Oncological treatment generally implies important aggression for the body. The drugs, radiotherapy and surgical procedures to which these patients are exposed12 can directly give rise to breathing difficulties.

Radiotherapy, as a result of the associated inflammation and posterior cicatrization, produces restrictive symptoms through direct action upon the lung parenchyma and surrounding structures, and alterations in gas diffusion across the alveolar-capillary membrane or barrier (the latter being destroyed and replaced by connective tissue).44,45 The clinical manifestations are rarely of an acute nature—the typical symptoms being dry cough with episodes that can be confused with bronchospasm.2 A fundamental element of care is the use of anti-inflammatory agents to improve the respiratory conditions of the affected children (inhalatory corticosteroids such as budesonide, for chronic prophylactic treatment, or systemic corticosteroids such as methylprednisolone, for the acute conditions).46

Chemotherapy is able to produce respiratory symptoms from the start of administration.44,45 A high degree of suspicion must be observed, since dyspnea is rarely attributed to cytostatic drug use, due to the fact that the previously described complications are comparatively much more frequent. It is therefore useful to be familiarized both with the typical presentations of this condition (Table 4) and with the factors that facilitate its development (very young patients, the use of concomitant or previous cranial irradiation, anthracycline use, and the application of chest irradiation).2 Management generally involves suspension of the drug treatment and provision of the supportive measures needed in each individual case (Table 4).2,44,45,50

The authors have no conflict of interest to declare.