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Progression of obstructive ventilatory disorder in Fabry disease: Only a matter of time?

We read with great interest the paper by Odler et al. regarding the respiratory involvement in patients with Fabry disease (FD). This is the first study to evaluate repetitive pulmonary function tests (PFTs) in five patients with FD on enzyme replacement therapy (ERT), with an average followup time of 5 years. The authors found that the main PFT alteration was moderate non-reversible obstructive ventilatory disorder and stabilization of airway obstruction during follow-up was observed during ERT in most patients, emphasizing the importance of this treatment in respect of pulmonary manifestations. In a recently published paper, we also evaluated the respiratory involvement in 18 consecutive adult patients with FD referring to the Nephrology Clinic of San Gerardo Hospital, Monza, Italy, from January 1, 2010 to December 31, 2013. Similarly to Odler et al., we observed mild respiratory symptoms in the majority of patients and, when main airway obstruction (defined as Forced Expiratory Volume in the 1st second (FEV1)/Forced Vital Capacity (FVC)< 0.70) in absence of causes other than FD was found, it was non reversible. However, differently from the previously cited study, main airway obstruction was not the primary PFT alteration we observed and early signs of airway obstruction (including lung hyperinflation, increased airways resistance, and small-airways obstruction) were the most common findings. These differences between the two cohorts might be explained by the higher proportion of men (4/7—57%—vs. 6/18—33%—) and the higher percentage of patients on ERT (5/7—71%—vs. 7/18—39%—) in the group described by Odler et al. compared to our report. As previously described in other studies, airway obstruction seems to be more common in men and positively related to the severity of the disease (ERT is usually started in patients with more severe systemic disease). As in the study by Odler et al., in 15 patients of our cohort (median age at first PFT 48 years, 33% males) we performed repetitive PFTs. Median [IQR] follow-up time was 4 [3-5] years, median [IQR] number of PFTs for each patient were 3 [2-3]. No statistically significant difference was observed between the first and last PFT in our group of patients, see Table 1. We also evaluated differences in PFTs follow-up values between patients on ERT (#6, 3 males) and patients not on ERT (#9, 2 males): no differences were found between groups. Differently from our cohort and the study by Odler et al., Magage et al. performed a longitudinal evaluation of PFTs only in FD patients not receiving ERT (39 subjects, median follow-up time 24 months). During the serial follow-up, the authors observed an age-dependent reduction of FVC and FEV1 values only in male patients, while in women only an increased small-airways obstruction could be observed during follow-up. These findings may lead to two considerations: (1) small-airways obstruction is an early sign of both pulmonary involvement at baseline, as observed in our study, and disease progression, as observed by Magage et al. (2) Male patients with FD without ERT show a more severe pulmonary involvement with main airway obstruction progression. In conclusion, no statistically significant difference in PFTs was observed between baseline and after a median 4-year follow-up in our cohort of patients with FD. Even when considering patients on ERT vs. patients not on ERT, no statistically significant difference was found. Therefore, we speculate that ERT may stabilize PFTs in more severe patients, as observed by Odler et al. Less severe patients (eg, women and patients that do not require ERT) might have a slow progression of the respiratory involvement, more evident in the small airways as described by Magage et al., which makes it difficult to appreciate within a short follow-up. Future studies should aim to conduct long-term followup and to better clarify the effect of ERT on pulmonary * Disclosures: The authors have no conflicts of interest in connection with this article.