A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis

Abstract

Background: Tobacco smoking is associated with a reduced risk of developing sarcoidosis, and we previously reported that nicotine normalizes immune responses to environmental antigens in patients with active pulmonary sarcoidosis. The effects of nicotine on the progression of pulmonary sarcoidosis are unknown.

Research question: Is nicotine treatment well tolerated, and will it improve lung function in patients with active pulmonary sarcoidosis?

Study design and methods: With local institutional review board approval, a randomized, double-blind, controlled pilot trial was conducted of daily nicotine transdermal patch treatment (21 mg daily) or placebo patch use for 24 weeks. The Ohio State University Wexner Medical Center and Cleveland Clinic enrolled 50 consecutive subjects aged ≥ 18 years with active pulmonary sarcoidosis, based on symptoms (ie, dyspnea, cough) and objective radiographic evidence of infiltrates consistent with nonfibrotic lung disease. Each study group was compared at 26 weeks based on repeated measures of FVC, FEV1, quantitative lung texture score based on CT texture analysis, Fatigue Assessment Score (FAS), St. George's Respiratory Questionnaire (SGRQ), and the Sarcoidosis Assessment Tool.

Results: Nicotine treatment was associated with a clinically significant, approximately 2.1% (70 mL) improvement in FVC from baseline to 26 weeks. FVC decreased by a similar amount (2.2%) in the placebo group, with a net increase of 140 mL (95% CI, 10-260) when comparing nicotine vs placebo groups at 26 weeks. FEV1 and FAS improved marginally in the nicotine-treated group, compared with those on placebo. No improvement was observed in lung texture score, FAS, St. George's Respiratory Questionnaire score, or the Sarcoidosis Assessment Tool. There were no reported serious adverse events or evidence of nicotine addiction.

Interpretation: Nicotine treatment was well tolerated in patients with active pulmonary sarcoidosis, and the preliminary findings of this pilot study suggest that it may reduce disease progression, based on FVC.

Clinical trial registration: ClinicalTrials.gov; No.: NCT02265874; URL: www.clinicaltrials.gov.

Keywords: FVC; fatigue; granuloma; human; interstitial lung disease; nicotinic receptor; randomized controlled trial.

Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract

Figure 1

Study recruitment and follow-up. max = maximum; PCP = primary care physician.

Figure 2

A, Average FVC (95% CI) according to randomized treatment group at baseline and study week 26. B, Average FVC (95% CI) difference at week 26.