Definition / diagnosis
The currently valid term COP (cryptogenic organising pneumonitis) describes, like the term BOOP (bronchiolitis obliterans organizing pneumonia) still current in German-speaking countries, one and the same clinical syndrome which is characterised histologically by an organising pneumonia with intraluminal organising fibrosis in the alveolar ducts and alveolar spaces. There is also a variable degree of bronchiolar intra-luminal polyps of granulation tissue (bronchiolitis obliterans) as well as an interstitial inflammatory reaction. The lesions show a patchy distribution with an apparently similar temporal development pattern. These histopathological changes may be seen in several pulmonary or extrapulmonary processes and may even be idiopathic. Among the diseases in which this histopathological pattern occurs are organising bacterial and non-bacterial infections, organising aspiration pneumonia, collagen disease and vasculitis, EAA, eosinophilic lung diseases, post–bone marrow transplantation, drug effects, organisation after the inhalation of toxic substances and chronic inflammatory bowel diseases.
Incidence
Exact figures on the incidence and prevalence are not currently available. COP affects men and women to the same extent, the mean age of onset of the disease is 55 years and non-smokers are affected almost twice as often as smokers.
Aetiology
The aetiology of COP is not currently known but an abnormal reparatory response to an initially inflammatory triggering mechanism is assumed.
Symptoms
The patients often report a respiratory infection that precedes their current symptoms and that did not disappear after repeat administration of different antibiotics. There are accompanying vegetative symptoms such as fever, weight loss, night sweats and myalgia. On laboratory investigations, the ESR, CRP and neutrophil count are often raised. On auscultation, crepitations may be heard either over a circumscribed area or, more likely, throughout the lungs. Lung function tests show restrictive ventilatory impairment to be the main finding, while in a minority of patients there is also obstructive ventilatory impairment. There is a variable degree of abnormal gas exchange with correspondingly impaired diffusion of CO and arterial hypoxaemia. The main radiological finding in COP is bilateral or unilateral, mainly patchy alveolar consolidation with corresponding demonstration of a positive air bronchogram. Nodular changes are also very common, while reticulonodular changes are rare. On HRCT, there is a subpleural or peribronchiolar distribution in 50% of all cases. The so-called tree-in-bud phenomonen is classically seen: a nodular condensation of centrilobular branching structure resembling a branch with blossoms. A ground glass appearance is also common. Bronchial carcinoma is an important differential diagnosis. The cellular differentiation of BAL often shows the picture of a CD8-dominant lymphocytosis, often with increased cell counts of neutrophil and eosinophil granulocytes. Alveolar macrophages often show foamy changes.
Treatment
The treatment of choice is steroids, and in most cases this will allow a return to the original state. Similar to the regimen shown for IPF, but taking into consideration the often higher steroid requirement in COP and a notoriously high recurrence rate if the steroids are tapered off too quickly (depending on the publication, in up to 50% of cases), the initial dose should be 1.0-1.5 mg/kg body weight of prednisone equivalent (maximum 100 mg/day) for 4-8 weeks. If there is a response, the dose can be reduced slowly to 0.5-1.0 mg/kg body weight over a period of 4-6 weeks. This maintenance dose should then be slowly reduced further no earlier than after 3 to 6 months. If there is no primary response or if high steroid doses are not tolerated, steroid-sparing additional medication (such as cyclophosphamide or azathioprine) should be given, preferably in combination with 0.25 mg/kg body weight of prednisone.