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.

James Chung-Man HO

Clinical Associate Professor

The University of Hong Kong

Peripubertal girls with varying androgen concentrations will have careful phenotype/genotype assessment, primarily to assess the relationship between urinary exosomal DENND1A.V2 and serum free testosterone concentrations.

Optional sample banking for later genetic analysis: At the time of study, the investigators will request consent/assent to bank saliva samples for later genetic analysis (e.g., if additional highly-promising gene candidates for adolescent hyperandrogenemia/PCOS are identified). If subjects and parents do not provide assent/consent that would allow specimens to be banked for later genetic analysis, the samples and the means of linking specimens to data will be destroyed (once analysis for all participants is completed).

Polycystic Ovary Syndrome

Hyperandrogenism

Puberty

The investigators will perform careful phenotyping in addition to hormonal assessments and assessments of DENND1A

Phenotype/genotype assessment

Center for Research in Reproduction

Urinary DENND1A.V2 as a Predictor of Pubertal Hyperandrogenemia

Body mass index normalized for age and gender

Serum luteinizing hormone (LH) measured at same time as free testosterone and fasting insulin

Serum insulin measured at same time as free testosterone and morning LH

We do not have current plans to share IPD

Chris McCartney

Associate Professor of Medicine

University of Virginia

Penn State University

Virginia Commonwealth University

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Tubes of blood for genetic analysis (20 ml of blood/subject)

Syndromic Obesity

Gastroentérologie et Nutrition Pédiatriques , Hôpital Trousseau

Phenotypic and Genotypic Characterization of Subjects With Syndromic Obesity: Identifying New Candidate Genes by Exome Sequencing (OBEXOME)

Phenotypic and Genotypic Characterization of Subjects With Syndromic Obesity: Identifying New Candidate Genes by Exome Sequencing

Assistance Publique - Hôpitaux de Paris

Institut National de la Santé Et de la Recherche Médicale, France

Assignment of study medication Each patient will receive, in order of admission to the study, a consecutive patient number and the corresponding study medication. The assignment of this medication was made before the start of the study, using a computer generated list. Patients will receive the 3,000 ppm chlorine dioxide base preparation with written and precise instructions on how to prepare and take the dilutions.
7.1 Dosage and route of administration. Medication: chlorine dioxide 3000 ppm. Fco x 150 cc. 10 ml of 3000 ppm chlorine dioxide are added to 1 liter of water, per day. One part is taken every hour, until the content of the bottle is finished (8 to 12 shots).
Both the original dioxide bottle and the preparation for the day should be kept refrigerated.

COVID-19

Each patient will receive the 3,000 ppm chlorine dioxide base preparation with written and precise instructions on how to prepare and take the dilutions.
: 10 ml of 3000 ppm chlorine dioxide are added to 1 liter of water, per day. One part is taken every hour, until the content of the bottle is finished (8 to 12 shots).

chinese/proline

Roflumilast in Non-CF Bronchiectasis Study (2019)

Urinary DENND1A.V2 as a Predictor of Pubertal Hyperandrogenemia

Phenotypic and Genotypic Characterization of Subjects With Syndromic Obesity: Identifying New Candidate Genes by Exome Sequencing (OBEXOME)

Determination of the Effectiveness of Oral Chlorine Dioxide in the Treatment of COVID 19

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