Bronchiolitis obliterans OP (BOOP), which has recently been called OP, is an unusual lung disease, which is histopathologically defined by the presence of granulation tissue (inflammatory cells, fibroblasts and loose connective tissue) in the lumen of the distal pulmonary airspaces (alveoli and alveolar ducts), and in the bronchiolar lumen (Bronchiolitis obliterans), which lead to plugging of the bronchiolar and alveolar lumen.
1 OP is considered a nonspecific response to many types of lung injury, including medications, toxins, radiation, connective tissue diseases, cancers, lung and bone marrow transplantation, chronic thyroiditis, alcoholic cirrhosis, inflammatory bowel disease and bacterial or virus infection.
1 It is defined as idiopathic OP or cryptogenic OP (COP) when no underlying cause is present or identifiable.
2OP related to influenza viral infection only has been characterised in a few case reports, in immunocompetent and immunocompromised patients.
3–6 The clinical behaviour observed in these patients does not seem to differ from OP due to other causes. However, to our knowledge, the radiographic and histological findings of OP associated to the novel pandemic influenza A (H1N1) virus have not been previously described. In our case series of 19 critical ill patients admitted to ICU because of respiratory failure and MV requirement due to severe novel A (H1N1) virus infection, 2 out of 19 developed OP. In order to establish novel influenza as the probable cause of OP in these two cases, other potential causes, including drugs, toxins and other infections, were considered, explored and excluded, leaving novel influenza as the most likely contributor.
OP remains a diagnosis of exclusion. Hence, once other most common diagnoses have been ruled out, interventional examinations should be conducted, if the patient's condition allows it, to make an early histological diagnosis and start proper treatment. BAL results are usually nonspecific, thus it is not considered of diagnostic value.
7 Therefore, considering transbronchial biopsy permits accurate diagnosis only in a minority of the patients, an OLB is the evaluation of choice in order to ensure OP diagnosis.
8 Interestingly, one of our patients was subjected to a CT as well as to an OLB while still being in prone position due to severe respiratory failure and no complication was observed.
The role of corticosteroids in the management of severely ill patients with novel influenza A (H1N1) virus infection is unclear and controversial. However, moderate-dose corticoids do not seem to increase the risks,
9 and might be helpful in the most severe cases. Therefore, driven by some clinical similarities with SARS, and severe community-acquired pneumonia,
10 11 we decided to treat all our severe patients with hydrocortisone from the ICU admission during a 7 days period. Whether this therapy was an actual contribution and in which amount, should be further evaluated in larger series.
Regarding OP treatment, it mainly consists in the administration of systemic corticosteroids, which induce frequently a rapid clinical improvement. Epler
et al1 suggested an initial dose of 1 mg/kg prednisone, but there are also data showing good results using only 0.5 mg/kg.
12 In our two cases, steroid therapy was very effective, too. However, we preferred a high-dose corticoid to ensure the clinical response of these two patients, because in both cases hydrocortisone treatment had been finished only recently when OP was diagnosed, and the severity of the first case required a rapid and intensive intervention. Given the evident improvement we observed in the first case with a steroid pulse therapy, we decided the second case should receive the same treatment. We cannot discard that a lower corticoids dose could have been equally effective in our patients.
When managing OP cases, it is generally suggested to continue therapy with corticosteroids for at least 6 months reducing the dose, but a common problem is relapse of disease when corticosteroids dosage is tapered off.
13 After 8 months, our two of patients are in good condition without relapsing, despite they finished prednisone at 6 months.
Different clinical types of pneumonia associated with influenza virus infection have been reported: influenza complicated by secondary bacterial pneumonia, primary influenza virus pneumonia and combined influenza virus and bacterial pneumonia.
14 Nevertheless, these cases suggest that OP should be kept in mind as other possible type of associated pneumonia, when treating patients who present this clinical behaviour following influenza-like illness by novel A (H1N1) virus infection.
The pathologic features of pulmonary influenza virus infection that have been described are as follows: necrotizing tracheobronchitis, enlargement and vacuolisation of respiratory epithelial cells, fibrinous pneumonia (diffuse alveolar damage), secondary bacterial pneumonia (especially pneumococcal) and Bronchiolitis obliterans with OP.
15–19These two cases provide clinical insight into lung involvement due to novel influenza. Although 19 confirmed patients with this new virus in the ICU setting may appear as a limited series, the development of OP in more than 10% of these patients excess by far the usual incidence of this rare disease, and suggests OP should be considered on the differential diagnosis of patients with severe novel influenza who present high fever and air space consolidation, without demonstrated infection, during in-hospital stay.
Learning points
- OP should be considered on the differential diagnosis of patients with severe novel influenza who present high fever and air space consolidation, without demonstrated infection, during in-hospital stay.
- OP remains a diagnosis of exclusion. Hence, once other most common diagnoses have been ruled out, interventional examinations should be conducted, if the patient's condition allows it, to make an early histological diagnosis and start proper treatment.
- Open lung biopsy is the evaluation of choice in order to ensure OP diagnosis. Inclusive in those patients with severe respiratory failure is feasible and relatively safe.
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