The mechanisms of idiopathic pulmonary fibrosis (IPF), a rare, devastating disease with a median survival of 3–5 years, are not fully understood. Gastroesophageal reflux disease (GERD) is a frequent comorbidity encountered in IPF. Hypothetically, GERD-associated microaspiration may lead to persistent inflammation impairing lung infrastructure, thereby possibly accelerating the progression of IPF. IPF may increase intrathoracic pressure, which can aggravate GERD and vice versa. On the basis of the possible beneficial effects of antireflux or antacid therapy on lung function, acute exacerbation, and survival, the recent international IPF guideline recommends antacid therapies for patients with IPF, regardless of symptomatic GERD. However, due to newer conflicting data, several national guidelines do not support this recommendation. Elucidation of these questions by further clinical and bench-to-bedside research may provide us with rational clinical diagnostic and therapeutic approaches concerning GERD in IPF. The present review aims to discuss the latest data on the controversial association of IPF and GERD.

Background Genetic variants of TOLLIP and MUC5B, both on chromosome 11, have been reported to be associated with the development and/or prognosis of idiopathic pulmonary fibrosis (IPF). This retrospective study was conducted to investigate the association of MUC5B and TOLLIP SNPs with disease outcome in IPF. 62 IPF patients and 50 healthy controls (HC) from our Institution were genotyped for SNPs within MUC5B (rs35705950) and TOLLIP (rs3750920 and rs5743890). Correlation of SNPs genotypes with survival, acute exacerbation (AE) or disease progression (defined as a decline of ≥ 5% in FVC and or ≥ 10% in DLco in one year) was investigated. Results The MUC5B rs35705950 minor allele (T) was more frequent in IPF subjects than in HC (35% vs 9% p < 0.001). TOLLIP SNPs alleles and genotype distribution did not differ between IPF and HC and did not vary according to gender, age, BMI and lung functional impairment at baseline. The minor allele (C) in TOLLIP rs5743890 was associated with worse survival and with disease progression in all performed analyses. The MUC5B rs35705950 or the TOLLIP rs3750920 minor allele, were not associated with disease progression or AE. Conclusion We confirm that the minor allele of MUC5B rs35705950 is associated with IPF. The minor allele of TOLLIP rs5743890 appears to be a predictor of worse survival and more rapid disease progression, therefore being of potential utility to stratify IPF patients at baseline.

Background: Immunosuppressive therapy still is the standard treatment for patients with connective tissue diseaseassociated interstitial lung disease (CTD-ILD). Objectives: This retrospective study aimed to provide data on the tolerability and efficacy of azathioprine in progressive CTD-ILDs. Methods: A total of 56 patients with CTD-ILD treated with azathioprine between 2003 and 2014 were included in the study. The patients were assessed every 3 months during follow-up. Results: The mean treatment duration was 34 months, with a range of 3-105 months. Fifteen patients (27%) discontinued treatment due to side effects, mostly due to elevated liver enzymes, within the first 3 months. Forty-one patients were treated for longer than 3 months, and 27 of those (66%) had stabilization or improvement of pulmonary function during treatment. In patients who remained stable or improved, the mean FVC was 62 ± 17% predicted (% pred) at initiation of treatment and 65 ± 17% pred at the last follow-up visit (p = 0.036), and the mean DLCO was 38 ± 16% pred at initiation of treatment and 39 ± 17% pred at the last follow-up visit (p = 0.06). Conclusions: Azathioprine can stabilize or improve CTD-ILD. While early drug intolerance is frequent, most patients who have tolerated the drug well achieve long-term stabilization or improvement of lung function.

Background: Anti-DFS70 antibodies, corresponding to the dense fine speckled antinuclear antibody (ANA) pattern in HEp-2 substrates, have been observed in chronic inflammatory conditions, cancer and in healthy individuals but in only a small percentage of patients with connective tissue diseases (CTD). Objectives: The study was aimed to investigate the possible role of Anti-DFS70 antibodies to distinguish CTD associated interstitial lung disease (CTD-ILD) from idiopathic interstitial pneumonia (IIP) and to explore potential correlations between anti-DFS70 antibodies and clinical parameters. Methods: Serum samples were collected from 49 healthy controls (HC), 35 scleroderma-ILD (SSc-ILD) patients as negative controls for anti-DFS70 antibody, and 260 patients with the initial diagnosis IIP including 100 nonspecific interstitial pneumonia (NSIP) and 160 idiopathic pulmonary fibrosis (IPF) patients. ANA pattern was identified by indirect immunofluorescence on HEp-2 cells and anti-DFS70 antibodies were measured in serum by ELISA. Results: Serum anti-DFS70 antibodies were less frequently seen in ILD and SSc-ILD patients compared to HCs. Thirty-seven patients (34 initial idiopathic NSIP and 3 initial IPF patients) developed CTD during 24 months of follow-up, most of them combined with ANA positivity and anti-DFS70 antibody negativity. Anti-DFS70 antibody positivity was not significantly different between CTD-ILD and idiopathic ILD. Conclusions: The frequency of serum anti-DFS70 antibody is markedly decreased in patients with ILDs. Anti-DFS70 antibodies may be useful to predict CTD development in ILD patients.