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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder of unknown aetiology that leads to death in the majority of patients within 3–5 years of diagnosis.1 One of the most prominent features of IPF is a persistent dry cough that affects 73–86% of patients.1 The aetiology of the cough is unknown but presumably linked to the lung fibrosis. Unfortunately, the cough is often disabling and resistant to traditional antitussive therapies.2
We present findings from a prospective cohort of 11 individuals with chronic cough caused by IPF who were enrolled in an open label phase II trial of thalidomide. Thalidomide was administered daily in 100–400 mg doses. Patients were followed with interval histories, physical examinations and quality of life questionnaires. Assessment and quantification of cough was recorded by subjects on question No 2 of the St George’s Hospital Respiratory Questionnaire (SGRQ): “Over the last 3 months, I have coughed: most days a week; several days a week; a few days a month; only with chest infections; not at all” as well as by subject report. Change in cough was measured with the SGRQ from baseline to 3 months and compared using the Wilcoxon matched pairs signed ranks test.3
Of the 11 patients enrolled in the study, all noted cough “most or several days a week” at baseline. During the course of the study, 10 noted marked to complete resolution of cough while receiving thalidomide (table 1). The cough score was 4.9 (0.3) at baseline and decreased to 2.2 (1.6) (p = 0.03) after 3 months of follow-up in six subjects for which there were complete data. Interestingly, three patients, who stopped taking thalidomide, all experienced return of the cough within 2 weeks. However, on reinstitution of thalidomide, all three patients again had resolution of the cough. In this study, the most common thalidomide associated adverse events were dizziness and constipation.
The aetiology of the cough associated with IPF is unclear. Although a significant number of patients with interstitial lung disease may have alternative reasons for their cough, nearly 50% have no other identifiable cause.4 Thalidomide, a drug with a tainted past due to causing teratagenic limb defects, has been “rediscovered” for its potent immunomodulatory, anti-inflammatory and antiangiogenic properties.5
We have described the resolution of IPF associated chronic cough with thalidomide in 10 patients with IPF. We believe this antitussive response to be a direct effect of the thalidomide, given the recurrence of the cough off the drug and suppression with resumption of thalidomide in three patients. The mechanism by which thalidomide suppressed the cough is unknown, but we hypothesise that it is due either to anti-inflammatory properties or a direct inhibitory effect on pulmonary sensory nerve fibres. As chronic cough has been associated with significant deterioration in patient’s quality of life, amelioration of the IPF cough with thalidomide may be beneficial for these patients with an incurable progressive disease.
In summary, our observations suggest that future clinical trials using low dose thalidomide for the suppression of cough in IPF are warranted.
Funding: The clinical trial in which the subjects of this observational cohort participated was investigator initiated and sponsored. Celgene Corporation was a supporter of the trial and provided monetary support for the trial. The authors have no financial or personal relationship beyond the clinical trial support with Celgene Corporation.
Competing interests: None.
Ethics approval: Ethics approval was obtained.