Oral roflumilast 250 microgram daily will be started at the baseline visit for 4 weeks. For those who can tolerate the initial 4-week treatment, roflumilast will be increased to 500 microgram daily, allowing subsequent dose reduction back to 250 microgram daily in case of CTCAE grade 3 or 4 toxicities.

Non-cystic Fibrosis Bronchiectasis

Roflumilast, a phosphodiesterase 4 (PDE4) inhibitor is approved worldwide (including Hong Kong) for treatment of severe chronic obstructive pulmonary disease (COPD) with frequent exacerbations. Roflumilast has been shown to have anti-inflammatory effect in patients with COPD, with significant reduction of sputum absolute neutrophil count, IL-8 and neutrophil elastase compared with placebo treatment. Roflumilast can also improve the lung function parameters in patients with COPD and reduce the rate of moderate-to-severe exacerbations.

Roflumilast Oral Tablet

Queen Mary Hospital

Roflumilast in Non-CF Bronchiectasis Study (2019)

Anti-inflammatory Effects of Roflumilast Treatment for 12 Weeks in Stable-state Non-cystic Fibrosis Bronchiectasis

Daily sputum volume is determined as the average of a three consecutive day collection (9:00 a.m. to 9:00 a.m.) at home, using clear pre-labeled sterile plastic (60 ml) pots stored at 4°C. Subjects are instructed and trained to completely empty the contents of their mouth before expectorating into the sputum pots to ensure minimal contamination by saliva and food debris. The volume of a 24-hour sputum specimen is determined as the volume of water (to the nearest 0.1 ml) in an adjacent identical pot containing water at the same level as the sputum in the sputum-containing pot.

A fresh sputum sample is collected in a sterile clear plastic pot after thorough mouth emptying on the day of planned clinic visit. Sputum leukocyte density is measured within 2 hours of collection by a designated technician, based on five aliquots chosen randomly from the center of a fresh specimen, which are then serially diluted with phosphate-buffered saline (PBS) and read with a light microscope and a hemocytometer as we previously described.

Fresh sputum sample is stored at −70° C within 15 min of collection until ultracentrifugation (100,000 g for 30 min at 4° C) to obtain the sol phase used for enzyme-linked immunoabsorbent assay of cytokines (IL-1β, IL-8, TNF-alpha, IL-17) and LTB4 levels using commercially available kits.

Sputum neutrophil elastatse is measured using a commercially available kinetic, chromogenic microtitre plate assay with succinyl-Ala-Ala-Pro-Val-p-nitroanalide (Bachem) as a substrate, as we previously described. A standard curve, constructed from known concentrations of purified elastase, is included in each assay.

Sputum for bacterial culture is saved and sputum bacterial load is measured at designated visits as described previously with modifications.

Patients' HRQoL will be measured by St. George's Respiratory Questionnaire Hong Kong Chinese version (SGRQ-HK). SGRQ-HK is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airway disease. It consists of 2 parts with 50 items. It addresses frequency and severity patients' symptoms, as well as activities that cause or are limited by breathlessness. The scores range from 0 to 100, with higher scores indicating more limitations. The minimally important difference is a mean change of 4 units for slightly efficacious treatment, 8 units for moderately efficacious change and 12 units for very efficacious treatment. SGRQ-HK has been validated in patients with bronchiectasis and is considered a valid and sensitive instrument for determining quality of life in bronchiectasis patients.

cystic fibrosis/proline

Roflumilast in Non-CF Bronchiectasis Study (2019)

Najkompletnija baza ljekovitog bilja potpomognuta znanošću