In this study we hypothesized a relationship between the MRC chronic dyspnea scale and the FF profusion scores in surgical lung biopsies from UIP/IPF patients at diagnosis, to the best of our knowledge for the first time. In addition we hypothesized a relationship between FF and functional parameters of disease severity and survival in our population studied. No statistically significant correlation between FF scores and the MRC score was observed. No significant correlation between FF scores and functional parameters of disease severity as well as survival was documented.
Previous studies have shown that the MRC scale, a non-invasive and simple clinical tool to estimate chronic dyspnea, is reliable in the estimation of the severity, progression and prognosis in IPF patients [7, 8, 10]. Furthermore, previous studies of our group detected also a relationship between the MRC scale and tissue infiltrating CD8+ T lymphocytes as well as CD8+ T lymphocytes recovered by bronchoalveolar lavage [28, 29] as well as a relationship between the MRC dyspnea and physiological parameters obtained during maximal and submaximal exercise testing known to reflect exercise limitation, disease severity and survival in IPF . Therefore, we assumed that the MRC score could also be related with the FF profusion score in IPF lung biopsies, which has been shown predictive of survival in previous studies [20, 21, 23, 24]. Nevertheless, the results of the current study do not support our hypothesis of a relation between this histopathologic characteristic of IPF and the degree of dyspnea.
To the best of our knowledge there is only one study examining the relationship between worsening dyspnea over time (6 months) and the FF profusion in pharmacologically treated UIP/IPF patients that apparently contradicts our results . However, in this study Collard and co-workers used a different dyspnea scale extending from 0 (no dyspnea) to 20 (dyspnea at rest) and the relationship between dyspnea and the FF profusion at initial evaluation of patients and before treatment initiation is not reported.
Regarding our second endpoint, no significant association was found between survival and the profusion of FF in surgical lung biopsies from patients with IPF, measured semiquantitatively by the two already described score systems: the Brompton and the Michigan score [21, 22]. Published studies show contradictory results: in agreement to our results, Flaherty and co-workers did not find the profusion of FF to be a significant predictor of survival for 99 patients with UIP by any method (the Michigan score, the Brompton score and the Denver score). Accordingly, Collard and co-workers did not find a relationship between survival and any individual histopathological feature, including the profusion of FF . Similarly, in a recent work Hanak and co-workers failed to detect any relationship between FF prevalence and survival in IPF patients . In contrast to the above, other investigators succeeded to detect a relationship between different methodologically obtained scores for the estimation of the FF profusion and survival [20, 21, 23, 24].
As far as the association between the profusion of FF and functional parameters is concerned, our results are similar to the ones of Enomoto and co-workers . The investigators who found a relationship between the extent of FF and functional parameters mostly examined changes of functional parameters over time such as the decrease in both DLCO and FVC measured at 6 and 12 months after biopsy  and the worsening in percent predicted FVC over 6 months of follow up . That is, the profusion of FF was not correlated with the initial pulmonary function status, but with their deterioration over time.
In order to explain these contradictory results, one notices following a critical and comparative analysis of reported studies differences that mainly concern the length of survival and the methods of assessing the FF profusion [23–26]. Indeed, median survival ranges between studies from 28.8 months  to 69 months  and to 78 months in the present one, and the scoring systems of profusion of FF are different between study groups varying from the semiquantitative methods including the Brompton, Denver, and the Michigan scores [20–22, 25] to more sophisticated quantitative methods based on measurements with analytic software [23, 24, 26].
Our explanation for the absence of a relationship of FF profusion and indices of severity and survival observed in this study might first relate to the fact that FF, are only one, though certainly the one with a major pathogenetic role, of all the histopathologic characteristics of UIP/IPF, and [2, 31] secondly, to the fact that the geographically limited (small tissue size) of the lung sampled may not necessary reflect the resultant of the histopathology derangement in individual cases. Consequently, the potential role of FF, sites of dynamic ongoing active injury in a chronic progressive interstitial lung disease as UIP/IPF is,  may better reflect the previously observed relationship with indexes of disease deterioration such as decrease of DLCO and FVC [21, 25] and dyspnea worsening .
On the other hand, progressive breathlessness, the most disabling symptom of IPF though multifactorial better reflects the overall of lung damage and its related consequences on lung mechanics and gas exchange . Thus, the finding of this study that the MRC dyspnea scale does not correlate with FF profusion could be explained by the fact that the defects in lung mechanics and gas exchange which manifest clinically with progressive exertional dyspnea might result from the entire combination of histological changes that characterize UIP/IPF and their geographical extension. Indeed, dyspnea scores are better shown to relate with histological parameters such as end-stage fibrosis and honeycombing [7, 11].
The major weakness of the present study is its relatively small number of patients and its retrospective design. However, it includes a homogeneous population of one academic department and its retrospective design is a valid approach for the study of a disease with low prevalence such as UIP/IPF. Prospective studies require very long period of observation. In addition, the survival rate of our patients is higher than that of patients included in other studies and this might relate: firstly to the very early stage disease of patients included as shown by the fact that 19 of them presented MRC score 1 and 2 and no patient with MRC 5 was included, due to the inability to perform lung biopsy in such severely ill patients, and secondly to the fact that most patients were treatment naïve or discontinued treatment on the first sign of infection. Regarding this ultimate it is well known that UIP/IPF is unresponsive to any immunosuppressive therapy which on the contrary leads unavoidably to severe and often terminal infective complications .