We appreciate the comments of H.E. Collard and T.E. King on our article 1. The American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus classification has been important in advancing clinical understanding of the idiopathic interstitial pneumonias 2. In that document, the clinical entity of nonspecific interstitial pneumonia (NSIP) was proposed as a provisional term only. As we have argued, we believe that using histological appearances alone to define separate clinical entities is unhelpful 1. Different histological patterns may occur in the same patient 3. Furthermore, conditions with a defined aetiology (e.g. hypersensitivity pneumonitis, connective tissue disease or familial pulmonary fibrosis) may give rise to either usual interstitial pneumonia (UIP) or NSIP in different patients 4–6.
By associating the histological lesion of NSIP with a clinical diagnosis of NSIP, the ATS/ERS consensus classification has blurred the distinction between idiopathic and secondary NSIP in the minds of many clinicians. This has led some to consider NSIP as a single disorder. We agree strongly with H.E. Collard and T.E. King that many cases of NSIP are due to either connective tissue disease or hypersensitivity pneumonitis. However, when reviewing the clinical data in such cases there are often ancillary features that point to the underlying diagnosis 7. Once secondary cases are excluded, there remains a large sub-group of NSIP patients who have a clinical phenotype that overlaps substantially with that of UIP/idiopathic pulmonary fibrosis (IPF). This group of patients have a sex distribution, smoking-exposure history, mode of clinical presentation, distribution of clinical signs and bronchoalveolar lavage cell differential that mirrors that of IPF/UIP 2, 8, 9. The distribution of disease on high-resolution computed tomography is also strikingly similar 10.
We therefore propose that idiopathic UIP and idiopathic NSIP, sharing a common clinical phenotype, form a spectrum of disease with a common pathogenesis. The pathogenetic mechanisms involved in the development and progression of IPF are complex and are likely to involve abnormalities in a number of the multiple pathways of normal wound healing 1. It seems likely that the balance of abnormalities in each of the key wound-healing pathways may vary between individuals. This variation is likely to be responsible for the range of clinical, radiological and pathological phenotypes observed in IPF.
Like H.E. Collard and T.E. King, we hope that future clinical and scientific research will further clarify these issues, as advances in our understanding of idiopathic pulmonary fibrosis can only be to the benefit of patients with this devastating and currently untreatable disease.
Statement of interest
None declared.
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