Idiopathic pulmonary fibrosis: present understanding and future options

The past decade has been extraordinarily fruitful for the study and management of idiopathic pulmonary fibrosis (IPF). The ability of physicians to make a clear and definitive diagnosis has greatly improved, and a proliferation of clinical studies has started to build an evidence base upon which rational treatment decisions can be built. Nevertheless, the challenges facing patients and physicians remain formidable. The number of people dying from pulmonary fibrosis in the USA has increased by 50% in just 10 yrs (1992–2003) (fig. 1). The 175,088 deaths in such a short period highlight the devastating nature of this attritional lung disease, putting it on a par with many cancers in terms of outcome [1, 2].

Figure 1.

Mortality rates for pulmonary fibrosis significantly increased in the USA between 1992 and 2003 [1]. ▪: males; •: females.

The progression of IPF over time is characterised by repeated, focal episodes of epithelial cell perturbation and subsequent established fibrosis occurring over many years, resulting in a pattern of histopathology that is both temporally and spatially heterogeneous. Because of the repeated epithelial cell perturbation over time, much of the pathology consists of fixed fibrosis when the patient first presents requesting advice, with relatively little pathology that is amenable to improvement in response to any therapy. The nature of the disease process, and the likely response to treatment, therefore, means that we must be careful to set limits on expectations (for physicians and patients alike) of what any treatment can achieve. Since cure is currently impossible, the treatment goal should be to stabilise the disease if possible or at the least reduce the rate of progression. The new treatments needed to meet this treatment goal are now starting to emerge after a decade of unprecedented research activity, with significant and highly encouraging increases in the size and number of clinical studies and with the incremental increase in knowledge about the behaviour of the disease that has been gained over the past decade. In this regard, in the period of 1989–1999 a total of 114 patients were enrolled in four IPF studies [3–6], whereas the following decade (2000–2010) saw almost 3,000 patients enrolled in 11 studies (fig. 2) [7–16].

Figure 2.

The number of patients enrolled in clinical studies of idiopathic pulmonary fibrosis (IPF) has increased substantially in the past decade compared to the previous decade [3–16]. Figure provided courtesy of L. Richeldi (University Modena and Reggio Emilia, Modena, Italy; personal communication).

With this background of realistic expectations coupled with increasing optimism for IPF, a series of articles has reviewed the substantial progress that has been made in the management of IPF, and asked what advances we can reasonably expect in the coming years. Valeyre [17] discussed the latest insights on diagnosis of IPF. Albera [18] considered which end-points are most useful for evaluating the efficacy of IPF treatments, while Costabel [19] provided an overview of the evaluation of clinical study data in IPF. Finally, Egan [20] reviewed some of the strategies that are to be considered when drug therapy is no longer of value. Their expert contributions indicate that there is room for cautious optimism in this difficult therapeutic area, and that we may be entering an era in which prevention of progression is a reasonable goal for drug therapy.