Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder of unknown cause with no effective treatment. Cough affects up to 80% of patients with IPF, is frequently disabling, and lacks effective therapy. OBJECTIVE: To determine the efficacy of thalidomide in suppressing cough in patients with IPF. DESIGN: 24-week, double-blind, 2-treatment, 2-period crossover trial. (ClinicalTrials.gov registration number: NCT00600028) SETTING: 1 university center. PARTICIPANTS: 98 participants were screened, 24 were randomly assigned, 23 received treatment (78.3% men; mean age, 67.6 years; mean FVC, 70.4% predicted), and 20 completed both treatment periods. MEASUREMENTS: The primary end point was cough-specific quality of life measured by the Cough Quality of Life Questionnaire (CQLQ). Secondary end points were visual analogue scale of cough and the St. George's Respiratory Questionnaire (SGRQ). For all measures, lower scores equaled improved cough or respiratory quality of life. RESULTS: CQLQ scores significantly improved with thalidomide (mean difference vs. placebo, -11.4 [95% CI, -15.7 to -7.0]; P < 0.001). Thalidomide also significantly improved scores on the visual analogue scale of cough (mean difference vs. placebo, -31.2 [CI, -45.2 to -17.2]; P < 0.001). In participants receiving thalidomide, scores from the total SGRQ, SGRQ symptom domain, and SGRQ impact domain improved compared with those of participants receiving placebo. Adverse events were reported in 74% of patients receiving thalidomide and 22% receiving placebo; constipation, dizziness, and malaise were more frequent with thalidomide. LIMITATION: This was a single-center study of short duration and small sample size focused on symptom-specific quality of life. CONCLUSION: Thalidomide improved cough and respiratory quality of life in patients with IPF. A larger trial is warranted to assess these promising results. PRIMARY FUNDING SOURCE: Celgene Corporation.

Use of a medication control officer to reduce bias in a clinical trial: lessons learned from the scleroderma lung study.

BACKGROUND: Scleroderma Lung Study (SLS) was designed to evaluate the efficacy and safety of oral cyclophosphamide (CYC) versus placebo taken for 1 year for scleroderma-associated interstitial lung disease. An independent medication control officer (MCO), usually a physician, at each center was assigned to monitor laboratory and clinical toxicity of study medication and regulate its dosing based on these results. By having an MCO who watched and managed toxicity, the study investigators were free to care for study patients and to assess study outcomes without the potential bias of knowing toxicity data (toxicity from cyclophosphamide is distinctive - cytopenias and hematuria in particular). PURPOSE: To assess the usefulness of an MCO, whose chief role was to maintain safety while retaining the blinding in the clinical trial. METHODS: Patients had safety laboratory testing every 2-4 weeks and results were sent directly to the MCO within 2 days of the test. Other clinical adverse events (AEs) were reported by the patient to a nurse coordinator who reported them to the MCO who then managed the AEs to preserve the blinding of investigators caring for the patients. The MCO was provided pre-determined algorithms for dose adjustments of test medication based on the presence and severity of laboratory abnormalities. RESULTS: Safety monitoring by the MCO was effective in the early detection of drug toxicity with provision of appropriate medical intervention on a timely basis. At the same time, investigator blinding appeared to be maintained. LIMITATIONS: The testing of MCO effectiveness in maintaining blinding and consistency was not defined as an a priori hypothesis and thus complete data relating to the efficacy of the MCO were not collected in a prospective fashion. CONCLUSION: An MCO and pre-specified monitoring and dosing guidelines, coupled with uniform pre-specified responses to AEs, may be used effectively to preserve investigator blinding and provide consistency in response to AEs in a clinical trial setting, even when AEs of the test medication are distinctive.

Sleep quality and health-related quality of life in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disorder resulting in irreversible scarring of the lung parenchyma. Although fatigue is a prominent symptom for patients with IPF, little is known about sleep quality in patients with IPF. METHODS: In this cross-sectional study of 41 patients with IPF from a prospectively designed cohort, we ascertained sleep quality by means of the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale. Health status, baseline demographics, and physiologic parameters were also assessed. RESULTS: Patients with IPF reported extremely poor sleep quality and high frequency of daytime sleepiness, which differs significantly from normal control populations. Further, poor sleep quality was not associated with body mass index, age, gender, or lung function. This population also demonstrated extremely poor health status in a number of domains, including physical function and vitality. Poor sleep quality (by the global PSQI) was significantly associated with decreased quality of life (QOL) in several domains, including role of physical function (r = - 0.58, p = 0.001), vitality (r = - 0.43, p = 0.015), and role of emotions (r = - 0.40, p = 0.023). CONCLUSIONS: Poor sleep quality is extremely common in patients with IPF and is not predicted by variables traditionally associated with sleep-disordered breathing. Further, poor sleep quality is associated with poor QOL. These findings suggest that systematic evaluation of the cause of poor sleep quality in IPF is merited.

Respiratory physiologic changes in pregnancy.

In summary, the major physiologic changes that occur in pregnancy are the increased minute ventilation, which is caused by increased respiratory center sensitivity and drive; a compensated respiratory alkalosis; and a low expiratory reserve volume. The vital capacity and measures of forced expiration are well preserved. Patients who have many lung diseases tolerate pregnancy well, with the exception of those who have pulmonary hypertension or chronic respiratory insufficiency from parenchymal or neuromuscular disease.