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IntroductionThere is growing evidence of the role of infection in the pathogenesis of Idiopathic pulmonary fibrosis (IPF). Azithromycin, a macrolide antibiotic, has antibacterial and anti-inflammatory activity and has shown to be beneficial in animal models of lung fibrosis. This study aimed to assess the effects of prophylactic Azithromycin on hospital admissions, rescue antibiotic use and lung function in IPF.MethodA retrospective analysis identified all IPF patients receiving a prophylactic prescription of 250 mg Azithromycin three times a week (Monday, Wednesday and Friday) between 2012 and 2017. An IPF diagnosis was made, according to international guidelines,1following multi-disciplinary team discussion. The use of immunosuppressive therapy, immunodeficiency or the use of other prophylactic antibiotics resulted in study exclusion.ResultsOne hundred and fifteen patients with IPF receiving prophylactic Azithromycin were identified. Thirteen already established on therapy and 5 who received other prophylactic antibiotics were excluded. The remaining 97 IPF subjects had a mean age of 66.05±11.25 years, were predominantly male (65%) with moderately severe disease (DLco 34%±9.5% predicted; FVC 70%±18% predicted). The majority (92%) of IPF patients tolerated Azithromycin, only 8 (8.25%) discontinued therapy due to side effects (tinnitus (n=1) and gastrointestinal intolerance (n=7)). One discontinued following lung transplant and 4 had therapy discontinued at the discretion of the prescribing clinician who felt there had been no subjective improvement. In the Pre-treatment twelve month period a total of 29 hospital admissions (0.30±06 per patient years) and 146 courses of antibiotics (1.50±1.70 per patient years) were recorded. In the same cohort a year after commencing prophylactic Azithromycin, there were 7 hospital admissions (0.08±0.3 per patient years) and 31 therapeutic antibiotic courses prescribed (0.36±0.8 per patient years) (p=0.0086, p<0.0001 respectively) (figure 1). Lung function rate of change over the 12 months preceding and following initiation of antibiotics was examined and there was no significant change in rate of decline in either FVC or DLco.ConclusionsThe present study has shown the beneficial effect of prophylactic Azithromycin in IPF patients, decreasing both hospital admissions and antibiotic usage, however, further randomised placebo controlled studies are needed to support and confirm our findings.[Figure]ReferenceRaghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med2011;183:788824.

IntroductionPulmonary hypertension commonly occurs in ILD, and is a malignant prognostic factor. Predicting mortality in this group remains problematic. We hypothesised that a combination of baseline demographics and longitudinal change in PFT’s and the biomarker brain-natriuretic peptide (BNP) would predict mortality in ILD-PH.MethodsDemographics, ILD subtype, PFTs, echocardiogram, and CTs were reviewed in consecutive patients undergoing right heart catheterisation (RHC) for suspected ILD-PH. Predictors of prognosis were evaluated in their ability to predict mortality using Cox proportional hazard analysis. A prognostic model was developed and tested in a derivation cohort and tested in a separate validation cohort.Results180 patients with confirmed PH formed the derivation cohort (mean pulmonary arterial pressure (mPAP) at RHC 37±9 mmHg; 50% male). At baseline, the strongest predictor of mortality was the underlying ILD diagnosis, with idiopathic pulmonary fibrosis or chronic hypersensitivity pneumonitis strongly associated with mortality (hazard ratio (HR):3.58, p<0.001). A relative decline in forced vital capacity (FVC) of 10% at 12–24 months after RHC predicted mortality (HR:3.20, p=0.001), and an increase in BNP at 12–24 months was also associated with mortality (HR:2.27, p=0.005). A prognostic model combining baseline and longitudinal change risk stratified patients into very-high risk, high-risk and moderate risk groups. In the derivation cohort, the high-risk group had a HR of 2.20 (p=0.01), and the very high-risk group a HR of 4.40 (p=0.001). 50 patients with confirmed PH made up the validation cohort (mPAP 37±9 mmHg; 46% male). The high-risk group had a HR of 3.60 (p=0.01) and the very high-risk group a HR of 8.17 (p<0.001).ConclusionA simple prognostic score using longitudinal change in FVC and BNP powerfully predicts mortality in ILD-PH, and could be used to prognosticate and help prioritise precious organ allocation in this challenging population.[Figure]

IntroductionPatients with interstitial lung disease (ILD) often have signs of pulmonary hypertension (PH) when assessed non-invasively. The presence of pulmonary hypertension (PH) at right heart catheter (RHC) is a negative prognostic factor; however, the impact of elevated pulmonary vascular biomarkers in the absence of PH is poorly understood. We hypothesised that pulmonary vascular disease biomarkers would predict mortality in patients without PH at RHC.MethodsDemographics, ILD subtype, PFTs, echocardiogram, and CTs were reviewed in consecutive patients undergoing right heart catheterisation (RHC) for suspected ILD-PH. Patients with a mean pulmonary arterial pressure (mPAP) <25 mmHg at RHC were studied. Predictors of prognosis were evaluated in their ability to predict mortality using Cox proportional hazard analysis.ResultsBetween 2005 and 2015, 68 patients (47% male) were evaluated that did not subsequently have PH (mPAP at RHC 19±4 mmHg; Pulmonary vascular resistance (PVR) 2.5±1.4 Wood units). On CT scanning main pulmonary artery diameter (MPAdiam) was 29.9±5 mm and main pulmonary artery to aorta ratio (MPAdiam:aa) was 0.97±0.1. Median brain natriuretic peptide (BNP) was 44[29–72] (normal <20 ng.L) and predicted right ventricular systolic pressure (RVSP) at echocardiogram was 48±13 mmHg. Forced vital capacity (FVC) was 62%±22% predicted. PVR as a continuous variable predicted mortality (hazard ratio (HR):1.35, p=0.02) per unit increase. A MPAdiam ≥32 mm was associated with mortality (hazard ratio (HR):3.02, p=0.001) as was MPAdiam:aa ratio ≥0.9 (HR:4.05, p=0.001). BNP ≥40 ng.L (HR:2.47, p=0.02) and a RVSP ≥40 mmHg (HR:2.74, p=0.02) also predicted mortality. MPAdiam and PVR (expressed as a continuous variable) remained independent predictors of mortality after adjusting for ILD diagnosis, forced vital capacity (% predicted) and age at RHC.[Figure]ConclusionEven in the absence of PH at RHC, elevated pulmonary vascular biomarkers are useful in risk stratification of patients suspected of having ILD associated PH.

BackgroundThere are no ILD specific guidelines on the use of ambulatory oxygen. The AmbOx trial is a multicenter, randomised, cross-over controlled trial (NCT02286063), to assess quality of life during two weeks on ambulatory oxygen compared to two weeks off oxygen, in patients with fibrotic ILD.MethodsIndividuals with fibrotic ILD whose oxygen saturation was normal at rest, but dropped to ≤88% on a 6MWT, with stable symptoms during a two week run-in period, were recruited and randomised. Primary outcome: health status assessed by King’s Brief ILD questionnaire (KBILD). A simple question on whether breathlessness had changed (better, same, worse) over the previous two weeks was a key secondary outcome. Patients‘ experiences with portable oxygen were explored through interviews in a subgroup. At the end of the four week trial period, patients were asked if they wished to continue with the ambulatory oxygen.ResultsOut of 84 randomised patients, 76 completed the trial. Mean age 64.5±1.1 years, 58 males, 53 ever smokers, FVC 73.3%±19.1%, DLCO 38.7%±12.8%. 43 patients had possible/definite IPF. Ambulatory oxygen, compared to no oxygen, was associated with improvements in total KBILD score (p<0.0001). At the end of the two weeks on oxygen, the majority of patients reported improved breathlessness (better:52/76 – same:23/76 – worse:1/76), compared to the two weeks on no oxygen (better 1/76 – same:57/76 – worse:18/76). On trial completion, 51/76 (67%) of patients chose to continue on ambulatory oxygen. On multivariate analysis, factors independently predictive of the patient’s decision to continue, included younger age (64.8 vs 72.8 years, p=0.002), more severe disease (CPI 55.5 vs 49.1, p=0.003) and patient’s global assessment of improvement in breathlessness (OR 3.2, p=0.018). Despite symptomatic improvements in the majority, ambulatory oxygen was also associated with a number of patient-reported challenges, explored in the patient interviews.