Correlation of cough with disease activity and treatment with cyclophosphamide in scleroderma interstitial lung disease: findings from the Scleroderma Lung Study

Chest. 2012 Sep;142(3):614-621. doi: 10.1378/chest.11-0801.


Background: Cough is a significant symptom in patients with scleroderma interstitial lung disease (SSc-ILD), affecting 73% of the 158 patients enrolled in the Scleroderma Lung Study (SLS), a multicenter randomized trial of oral cyclophosphamide (CYC) vs placebo (PLA) in patients with active interstitial lung disease.

Methods: We examined the correlation of cough frequency and severity and phlegm production at baseline in 156 SLS participants with other baseline variables representing SSc-ILD disease activity and the cough response to 1 year of treatment with CYC vs PLA.

Results: Patients with cough at baseline had significantly lower diffusing capacity of the lung for carbon monoxide, dyspnea, the quality-of-life physical component summary, and the maximal fibrosis score on high-resolution CT imaging compared with those without cough at baseline. Cough severity and frequency correlated with FVC % predicted. After 12 months of treatment, cough frequency decreased in the CYC group compared with the PLA group and was significantly different from the PLA group at 18 months (6 months after discontinuation of CYC). However, the decreases in cough frequency did not correlate with the changes in FVC or diffusing capacity of the lung for carbon monoxide observed in the CYC group. Treatment-related improvements in cough frequency, as well as in FVC, were no longer apparent 12 months after discontinuation of CYC.

Conclusions: Cough is a common symptom in SSc-ILD and correlates with the extent of fibrosis. Cough frequency decreases significantly in response to treatment with CYC but returns to baseline 1 year after withdrawal of treatment. Cough may be a symptom of ongoing fibrosis and an independent variable in assessing therapeutic response to CYC.

Trial registry:; No.: NCT000004563; URL:

Trial registration: NCT00004563 NCT00004563.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cough / epidemiology*
  • Cyclophosphamide / therapeutic use*
  • Double-Blind Method
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lung Diseases, Interstitial / complications*
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / physiopathology
  • Prevalence
  • Pulmonary Diffusing Capacity / physiology
  • Pulmonary Fibrosis / physiopathology
  • Quality of Life
  • Respiratory Function Tests
  • Scleroderma, Systemic / complications*
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / physiopathology
  • Severity of Illness Index*
  • Treatment Outcome
  • Vital Capacity / physiology


  • Immunosuppressive Agents
  • Cyclophosphamide

Associated data