Background/Purpose: While chronic cough occurs in the majority of patients with systemic sclerosis-related interstitial lung disease (SSc-ILD),¹ its impact on quality of life has not been adequately addressed. Furthermore, minimal literature exists on the relationship between cough and SSc-ILD treatment response. This study uses data from the Scleroderma Lung Study (SLS) II to evaluate the disease burden of cough in SSc-ILD and to determine whether cough changes in response to treatment for SSc-ILD.

Methods: SLS II randomized adult SSc-ILD participants to mycophenolate (MMF) for 2 years (N=69) versus oral cyclophosphamide (CYC) for 1 year followed by 1 year of placebo (N=73). The primary outcome was FVC%-predicted and key secondary outcomes included frequent cough, as assessed by the St. GeorgeÕs Respiratory Questionnaire (SGRQ), along with breathlessness, quantitative extent of ILD (QILD) and fibrosis (QLF) on HRCT imaging and cough-specific quality of life (QOL), as assessed by the Leicester Cough Questionnaire (LCQ).

Results: The majority of participants (61%) reported frequent cough at baseline, of whom 66% also had moderate-severe GERD. Compared with those without cough, participants with frequent cough more often had GERD (p=0.025) and had increased breathing difficulty, lower DLCO and greater QLF in the whole lung (WL) and greater QILD in the WL and the lobe of maximal involvement (LM). LCQ scores were significantly correlated with dyspnea, general QOL measures, severity of GERD and QILD/QLF (all P<0.05). A 42% reduction in the proportion of participants with frequent cough occurred over the 24-month trial with no difference noted between treatment arms or between those with/without GERD at baseline (See Figure 1). However, patients in whom frequent cough persisted at 2 years were more likely to have developed GERD compared with patients who had resolution of frequent cough at 2 years (P=0.03). Logistic regression demonstrated associations between a reduction in cough and improvements in FVC%-predicted (P=0.06), breathlessness (P=0.02), and QILD-WL (P=0.03) at 24 months.

Conclusion: The majority of SLS II participants experienced frequent cough that was significantly associated with the severity of GERD, physiologic and radiographic measures of extent of ILD and non-cough specific QOL. After SSc-ILD treatment, participants experienced a significant reduction in cough, which correlated with improvements in physiologic and radiologic outcomes. These findings suggest that changes in cough may serve as a surrogate measure of treatment response in SSc-ILD. However, the development of GERD may diminish improvement in cough with SSc-ILD therapy. References: 1. Theodore, et al. Chest 2012;142:614-21.

Figure 1. Changes in the proportion of patients with frequent cough for patients with and without reflux at baseline.