Definition / diagnosis
According to the consensus conference, the group of NSIP is provisional. Originally conceived as an umbrella term for all otherwise non-classifiable forms of IIP, NSIP has been an entity in its own right since the last consensus conference and is based on the histopathological demonstration of an NSIP pattern, which shows a wide spectrum ranging from predominance of a chronic interstitial inflammation (cellular NSIP) to predominance of interstitial fibrosis (fibrotic NSIP). In contradistinction to the UIP pattern, the changes all appear to have the same age, with a predominantly homogeneous interstitial fibrosis of variable density. Intra-alveolar fibrotic processes are found in about one third of cases; fibrosis nests, as seen in UIP, are completely absent. Patients with a predominantly fibrosing reaction have a much worse prognosis compared with patients with a predominant inflammatory reaction. An additional complication is that the NSIP pattern is not specific for (idiopathic) NSIP but can also be seen in other syndromes, e.g. in collagen diseases, drug-induced pulmonary fibrosis and EAA. Thus, in pure clinical terms, it is much more difficult to classify than, for example, IPF and is based on the progression, cell findings on BAL and the HRCT.
There are currently no reliable data on the incidence, but it is probably lower than the incidence of IPF. NSIP patients are usually between 40 and 50 years old at the time of the initial diagnosis and thus almost 10 years younger than patients with IPF. There is no sex difference in the incidence of NSIP.
The aetiology of NSIP is currently completely unknown but it is worth stressing that in the above-mentioned cases of familial IPF isolated mutation carriers predominantly have an NSIP pattern. A discordant picture is also found time and again in IPF patients with evidence of an NSIP pattern as well as a UIP pattern in one and the same lung (in which cases they should, by definition, be considered as IPF). Lastly, cases have also occasionally been described where initially as part of VATS there is an NSIP pattern and then later at the time of transplantation a UIP pattern. It is thus not currently excluded that NSIP is a somewhat different response by the lung to one and the same triggering mechanism. This is also supported by the differentiation already discussed between the cellular and fibrotic NSIP, in which fibrotic NISP may indeed have a clinical course that resembles IPF, while cellular NSIP often responds to steroids and prognostically is much more favourable.
For NSIP, there is also mainly an insidious onset but courses with subacute forms are also occasionally possible. In addition to the initially prominent symptoms that are also found in IPF (exertional dyspnoea, cough), NSIP patients also have fatigue and, in at least 50%, weight loss. Fever is also present in a small percentage. Watch-glass nails and finger clubbing also occur but overall are less common than in IPF. Smokers are not disproportionately affected by the development of NSIP. Otherwise, the symptoms are similar to the clinical examination findings and also the results of lung function tests found for IPF. The heterogeneity of this patient group can be followed in many ways. BAL shows either a neutrophilic or lymphocytic alveolitis (the incidence for each being approximately 50%). Radiologically, NSIP patients noticeably have above all a ground glass appearance as the main finding on the HRCT; these are generally predominantly symmetrical and in a subpleural location. Irregular lines and increased reticular markings are found in about half of all patients; traction bronchiectasis then also occurs. Consolidation is not very typical but may well occur in the later course. Depending on the presence of fibrosing changes, a honeycomb pattern on HRCT may also be seen and the radiological picture is then difficult to differentiate from that of UIP. Accordingly, not even experienced radiologists can reliably differentiate it from UIP (32% of cases), EAA (20% of cases), organising pneumonia (14%) and other diagnoses (12%).
In NSIP patients with a progressive course a trial of treatment with steroids combined with azathioprine or cyclophosphamide should be undertaken in a similar way to the recommendations for IPF. NSIP patients with lymphocytic alveolitis and a predominant ground glass appearance (cellular NSIP) generally respond well to this type of treatment. As with IPF, secondary pulmonary hypertension may also be observed in the advanced stage of NSIP. Its pharmacological correction needs to be the subject of future studies.