Birgitta Versluijs

32 Pulmonary complications of HCT lung becomes a target for cytotoxic and immunemediated attack. 35 Cumulative incidence of IPS in children is estimated at 5-10%. 36,37 Treatment of IPS generally includes suppor- tive care and systemic corticosteroids. 35 Prognosis is poor with reported mortality rates of 50%-75%. 36,37 Bronchiolitis Obliterans Syndrome (BOS) is typically seen months after HCT. It is de- fined as chronic obstructive lung disease with PFT abnormalities (Forced expiratory vo- lume in 1 sec (FEV1) < 75% of predicted and FEV1/forced vital capacity (FVC) ratio < 0.7) and signs of air trapping and ground glass on high–resolution computed tomography. Patients with BOS may be asymptomatic but typically present with cough, wheezing or dyspnoea on exertion. Incidence of BOS in paediatric HCT is 4-9%, mortality ranges between 11-67%. 38,39 Both in IPS and in BOS, pre-HCT lung damage by conditioning regimen or infection attenuated by immune mediated processes lead to the actual lung disease, which can be regarded as pulmonary GVHD. Treatment consists of stepping up immunosuppression. 39,40 Primary pulmonary vascular complications of HCT are rarely seen. Pulmonary Arterial Hypertension (PAH) has a relation with thrombotic microangiopathy, a severe compli- cation of HCT in which toxic endothelial injury causes microangiopathy leading to mi- crothrombi and end organ injury, mostly in the kidneys but sometimes also affecting lungs. 41,42 PAH may also develop secondary to left sided heart disease, hypoxia and in- terstitial lung disease. The true incidence of PAH in children after HCT is unknown. Transthoracic echocardiography is recommended in any patient with unexplained hypo- xemic respiratory failure after HCT. 41 Pulmonary Veno-Occlusive Disease (VOD) is a very rare event, occurring early after HCT, with a suggested association with hepatic VOD. Several groups have studied long-term lung function among HCT survivors in detail. 38,43,44 Both obstructive lung disease and restrictive lung disease are observed. A triphasic mo- del has been suggested for chronic lung injury after HCT. First, alloantigen recognition takes place and initiates an influx of inflammatory cells, and then the persistence of this inflammatory signal makes lymphocytes migrate into the airway mucosa and contribute to epithelial injury. Subsequently, lung fibroblasts increase in number and lead to enhan- ced production of collagen. 45 Restrictive lung disease has been described in 10-33%, either as an isolated finding or in combination with decreased diffusion capacity of carbon monoxide (DLCO). 38,43 Ge- nerally speaking these findings are seen early after HCT and show some improvement 1-2 years after HCT and stabilize, but do not return to pre-HCT values. Risk factors for restrictive lung disease are certain cytotoxic agents and irradiation. Skin GvHD leading to scleroderma, chest wall deformities, short stature and respiratory and skeletal muscle 2