Improved Cough and Cough-Specific Quality of Life in Patients Treated for Scleroderma-Related Interstitial Lung Disease: Results of Scleroderma Lung Study II

Chest. 2017 Apr;151(4):813-820. doi: 10.1016/j.chest.2016.11.052. Epub 2016 Dec 22.


Background: Cough is a common symptom of scleroderma-related interstitial lung disease (SSc-ILD), but its relationship to other characteristics of SSc-ILD, impact on cough-specific quality of life (QoL), and response to therapy for SSc-ILD have not been well studied.

Methods: We investigated frequent cough (FC) in patients with SSc-ILD (N = 142) enrolled in the Scleroderma Lung Study II, a randomized controlled trial comparing mycophenolate mofetil (MMF) and oral cyclophosphamide (CYC) as treatments for interstitial lung disease (ILD). We determined the impact of FC on QoL (Leicester Cough Questionnaire [LCQ]), evaluated the change in FC in response to treatment for SSc-ILD, and examined the relationship between gastroesophageal reflux disease (GERD) and cough during the trial.

Results: Study participants who reported FC at baseline (61.3%) reported significantly more dyspnea, exhibited more extensive ILD on high-resolution CT, had a lower diffusing capacity for carbon monoxide, and reported more GERD symptoms than did those without FC. Cough-specific QoL was modestly impaired in patients with FC (total LCQ score, 15.4 ± 3.7; normal range, 3-21 [higher scores indicate worse QoL]). The proportion of patients with FC at baseline declined by 44% and 41% over 2 years in the CYC and MMF treatment arms, respectively, and this decline was significantly related to changes in GERD and ILD severity.

Conclusions: FC occurs commonly in SSc-ILD, correlates with both the presence and severity of GERD and ILD at baseline, and declines in parallel with improvements in both ILD and GERD over a 2-year course of therapy. Frequent cough might serve as a useful surrogate marker of treatment response in SSc-ILD trials.

Trial registry:; No.: NCT00883129; URL:

Keywords: cough; health-related quality of life; immunosuppressive therapy; interstitial lung disease; scleroderma.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Cough / drug therapy*
  • Cough / etiology
  • Cyclophosphamide / therapeutic use*
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Gastroesophageal Reflux / complications
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lung Diseases, Interstitial / complications
  • Lung Diseases, Interstitial / drug therapy*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Quality of Life*
  • Respiratory Function Tests
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / drug therapy*
  • Severity of Illness Index
  • Treatment Outcome


  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Mycophenolic Acid

Associated data