No abstract

Background Fibrotic interstitial lung disease (ILD) is often associated with poor outcomes, but has few predictors of progression. Daily home spirometry has been proposed to provide important information about the clinical course of idiopathic pulmonary disease (IPF). However, experience is limited, and home spirometry is not a routine component of patient care in ILD. Using home spirometry, we aimed to investigate the predictive potential of daily measurements of forced vital capacity (FVC) in fibrotic ILD. Methods In this prospective observational study, patients with fibrotic ILD and clinical progression were provided with home spirometers for daily measurements over 6 months. Hospital based spirometry was performed after three and 6 months. Disease progression, defined as death, lung transplantation, acute exacerbation or FVC decline > 10% relative was assessed in the cohort. Results From May 2017 until August 2018, we included 47 patients (IPF n = 20; non-IPF n = 27). Sufficient daily measurements were performed by 85.1% of the study cohort. Among these 40 patients (IPF n = 17; non-IPF n = 23), who had a mean ± SD age of 60.7 ± 11.3 years and FVC 64.7 ± 21.7% predicted (2.4 ± 0.8 L), 12 patients experienced disease progression (death: n = 2; lung transplantation: n = 3; acute exacerbation: n = 1; FVC decline > 10%: n = 6). Within the first 28 days, a group of patients had high daily variability in FVC, with 60.0% having a variation ≥5%. Patients with disease progression had significantly higher FVC variability than those in the stable group (median variability 8.6% vs. 4.8%; p = 0.002). Cox regression identified FVC variability as independently associated with disease progression when controlling for multiple confounding variables (hazard ratio: 1.203; 95% CI:1.050–1.378; p = 0.0076). Conclusions Daily home spirometry is feasible in IPF and non-IPF ILD and facilitates the identification of FVC variability, which was associated with disease progression.

Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity and pharmacokinetics of POS-Liq vs POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently. Twenty-four consecutive LTx-recipients with 191 documented posaconazole trough levels (PTLs) for POS-Liq or POS-Tab were included. The administered daily doses were 300 mg for POS-Tab and 600 mg (prophylaxis) or 800 mg (therapy) for POS-Liq. Target PTLs were ≥700 ng/mL (prophylaxis) and ≥1250 ng/mL (therapy). The overall prophylactic and therapeutic response rates were 78% and 67%, respectively. No cases of hepatotoxicity or QT-prolongation were observed with either formulation. The achieved target PTLs were tripled under POS-Tab compared to POS-Liq with fewer risk factors for sub-therapeutic PTLs. Concomitant administration of POS-Tab significantly reduced the tacrolimus concentration-to-dose ratio (P = .001). We suggest the use of POS-Tab is appropriate for prophylaxis and therapy of Aspergillus infections in LTx-recipients, since POS-Tab displayed more reliable PTLs with no added adverse events. However, we recommend regular drug monitoring for POS-Liq and for therapy with POS-Tab and that immunosuppressant levels are monitored closely when the posaconazole formulation is switched.