Correlation of Early Cough with Disease Activity measured by High-resolution CT in ATLAS: a Phase 1b Study of Inhaled Pirfenidone in Idiopathic Pulmonary Fibrosis

<bold>Background:</bold> Cough is a prevalent symptom of IPF. While the manifestation of early cough (EC) may relate to a response to the nebulization procedure, its correlation with structural characteristics may reveal another underexplored etiology <bold>Aims:</bold> This study aimed to explore the incidence and implications of EC in a cohort of 91 subjects with IPF enrolled in the phase 1b AP01-002 clinical trial (ATLAS) of aerosolized pirfenidone <bold>Methods:</bold> Among 70 participants who underwent baseline and 24-week high-resolution CT (HRCT) scans, 69 were deemed acceptable in image quality. Participants were categorized by the onset day of cough: EC (≤10 days), late cough (>10 days), and no cough. Quantitative assessments of ground glass (QGG) and lung fibrosis (QLF) were derived from HRCT. Multivariable linear regressions assessed the relationship between cough and HRCT changes. The distribution of participants reporting EC, late cough, and no cough was 14.5% (N=10), 15.9% (N=11), and 69.6% (N=48), respectively. Mean (SD) HRCT changes in the EC, late, and no cough groups were -2.5% (6.0), -0.1% (4.1), and 1.2% (3.1) for QGG, and -1.2% (6.2), 2.4% (3.2), and 0.8% (5.7) for QLF, respectively. Participants with EC were predominantly female, had less extensive ILD at baseline HRCT, and showed significant reductions in QGG compared to those without cough (p=0.034, 95% CI [−6.2, -0.3]). No significant changes in QLF were observed with EC. <bold>Conclusions:</bold> EC was associated with a reduction in ground glass opacities at week 24, thought to represent an inflammatory process. Early cough may serve as a useful surrogate marker of treatment response.