Effects of Pirfenidone on Idiopathic Pulmonary Fibrosis Progression and Safety: Results of Multicenter Prospective Observational Study.

The aim of this study was to determine the effectiveness of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) seen in clinical practice. Fifty-five adults with IPF were enrolled in this multicenter, open-label, non-randomized, non-controlled, interventional clinical study. All patients received pirfenidone 2403 mg/day (three 267 mg capsules three times daily) for 26 weeks. After 26 weeks of treatment, the mean change in absolute forced vital capacity (FVC) was 128.8 mL (95% confidence interval [CI] -26.8, 284.4) and the mean change in relative predicted FVC was -0.10% (95% CI -3.18, 2.99). Stable disease (defined as improvement of ≥0% or a decline of <10% to 0% of the corresponding FVC value) was observed in most patients (relative FVC, 90.9%; absolute FVC, 83.6%). There was no statistically significant change in the mean high-resolution computed tomography fibrosis score or lung opacity score at week 26 compared with baseline. Treatment-emergent adverse events were reported in 80% of patients during the treatment period; most of them were mild or moderate in severity. No serious pirfenidone-related adverse events were observed during the study period. Pirfenidone was generally safe and effective for controlling functional decline and stabilizing disease in patients with IPF encountered in clinical practice in Russia.

Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS: In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 µg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS: In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS: In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).

Pulmonary alveolar proteinosis: a long way to correct diagnosis: problems of diagnostics and therapy in routine practice.

Pulmonary Alveolar Proteinosis is a rare disease with unknown etiology that is due to an abnormal surfactant metabolism. Retrospective analysis of a consecutive series of 68 patients with PAP who were seen at Pulmonology Clinic of Pavlov State Medical University from 1977-2013 was performed. The mean time since first abnormalities were found until diagnosis establishment was 34 months. During that time, most patients were treated with antibiotics, tuberculostatics, glucocorticoids, and immunosupressants. The most effective PAP treatment method was found to be whole lung lavage procedure: 82% of patients showed improvement after its implementation. Delayed diagnosis and incorrect administration of antibiotics, tuberculostatics etc. reduce the probability of a long symptom-free period after lung lavage and spontaneous resolution of the disease.