Clinical trial NCT03467035: Role of NLRP3 Inflammasone and Hypoxia in the Severity of Osteoporosis in Patients With Bronchiectasis
Official title: Role of NLRP3 Inflammasone and Hypoxia in the Severity of Osteoporosis in Patients With Bronchiectasis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bronchiectasis Adult
Osteoporosis, Osteopenia
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2018-03-15
Enrollment: 80
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 80 adult patients with proven bronchiectasis, diagnosed by high-resolution computed tomography (HRCT), will be recruited from our outpatient clinic of Chang Gung Memorial Hospital with written informed consent. The inclusion and exclusion criteria are described above.

Brief summary: The objectives of this research grant are to determine the association of hypoxia with the severity of osteoporosis in the patients with bronchiectasis and whether the mechanism of inflammation is triggered by inflammasones, which makes it more prone to osteoporosis in patients with bronchiectasis.

Detailed description: 80 patients with proven bronchiectasis, diagnosed by high-resolution computed tomography (HRCT), will be recruited from our outpatient clinic of Chang Gung Memorial Hospital with written informed consent. Inclusion criteria are: daily sputum \> 10 ml; absence of asthma or other unstable systemic diseases; and "steady-state" bronchiectasis (\< 10% alteration of 24 h sputum volume, FEV1, and FVC, and in the absence of deterioration in respiratory symptoms at baseline visits). Exclusion criteria include: unreliable clinic attendance; regular user of inhaled or oral corticosteroids; history of lung resection and known asthma defined according to American Thoracic Society guidelines.

The lung function and desaturation will be assessed by six-minute walking tests and the severity of disease will be evaluated by HRCT scores. Peripheral blood sample (40ml/person) is performed to analyze the bone turnover markers and the level of Hif in PBMC.

Eligibility criteria: Inclusion Criteria:

1. willing to sign a written consent form
2. Male and female subjects with bronchiectasis diagnosed by high-resolution computed tomography
3. willing to accept 6-minute exercise pulmonary function test and blood draw
4. Men and women over the age of 20
5. Has undergone chest computed tomography and bone density examination in the recent five years

Exclusion Criteria:

1. pregnant women or lactating women
2. asthma, lung resection history before the screening period
3. active Tuberculosis infection
4. Have received oral steroid treatment within 30 days
5. current acute attack or clinical symptoms instability of bronchiectasis

Primary outcomes:
measure: six minute walk test
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Chung Memorial Hospital
name: Chun-Hua Wang
role: STUDY_DIRECTOR
References:
citation: Cole PJ. Inflammation: a two-edged sword--the model of bronchiectasis. Eur J Respir Dis Suppl. 1986;147:6-15.
citation: Arnett TR. Acidosis, hypoxia and bone. Arch Biochem Biophys. 2010 Nov 1;503(1):103-9. doi: 10.1016/j.abb.2010.07.021. Epub 2010 Jul 23.
citation: Utting JC, Flanagan AM, Brandao-Burch A, Orriss IR, Arnett TR. Hypoxia stimulates osteoclast formation from human peripheral blood. Cell Biochem Funct. 2010 Jul;28(5):374-80. doi: 10.1002/cbf.1660.
citation: Kim RY, Pinkerton JW, Gibson PG, Cooper MA, Horvat JC, Hansbro PM. Inflammasomes in COPD and neutrophilic asthma. Thorax. 2015 Dec;70(12):1199-201. doi: 10.1136/thoraxjnl-2014-206736. Epub 2015 Oct 22. No abstract available.
citation: Diehl N, Johnson MM. Prevalence of Osteopenia and Osteoporosis in Patients with Noncystic Fibrosis Bronchiectasis. South Med J. 2016 Dec;109(12):779-783. doi: 10.14423/SMJ.0000000000000565.
citation: McDonnell MJ, Aliberti S, Goeminne PC, Restrepo MI, Finch S, Pesci A, Dupont LJ, Fardon TC, Wilson R, Loebinger MR, Skrbic D, Obradovic D, De Soyza A, Ward C, Laffey JG, Rutherford RM, Chalmers JD. Comorbidities and the risk of mortality in patients with bronchiectasis: an international multicentre cohort study. Lancet Respir Med. 2016 Dec;4(12):969-979. doi: 10.1016/S2213-2600(16)30320-4. Epub 2016 Nov 16.