By performing a low-dose CT in patients with primary spontaneous pneumothorax (PSP) the typical pulmonary abnormalities, related to the mutation in FLCN, are detected. Patients will be tested for the FLCN mutation by performing a blood sample for…
ID
Bron
Verkorte titel
Aandoening
pneumothorax, birt hogg dube syndrome, renal cell carcinoma
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
The prevalence of CT abnormalities possibly related to Birt-Hogg-Dubé syndrome in subjects presenting with a 'primary' spontaneous pneumothorax.
Achtergrond van het onderzoek
Over 15% of all kidney tumours are related to germline mutations. Part of this is caused by the autosomal dominant mutation in the folliculin (FLCN) gene. This mutation is responsible for a number of phenomena that are all, or in part, present in the carriers of the mutation resulting in Birt-Hogg-Dubé-syndrome. This hereditary syndrome is characterized by fibrofolliculomas, lung cysts and renal cell cancer (RCC). The cysts can easily rupture resulting in a pneumothorax. 5-10% of spontaneous pneumothorax (SP) patients may have a mutation in the FLCN gen. Standard diagnostic test for primary spontaneous pneumothorax (PSP) is chest X-ray, CT is only performed on indication. The characteristic lung cysts of BHD are only clearly visible on CT. Approximately 35% of the BHD carriers develop one or more kidney tumours (RCC). Determining carrier status offers opportunities for identification of family members who, in the presence of the mutation, are also at risk for developing RCC. For the detection of new BHD carriers there is no standard research, patients are found by symptoms, and through them family members with this mutation. A potentially effective alternative way of detecting a large proportion of the BHD patients may be the standard examination of SP patients with CT and screening a blood sample through next generation sequencing (NGS). This is still supported by the high frequency of pneumothorax as the first symptom of BHD syndrome, up to 65% of the BHD population develops pneumothorax. The VUMC database shows that in a cohort of 115 carriers with 5 years of follow-up, 2 new RCCs were found, the frequency being 0.3 / 100 man-years, and moreover, per discovered carrier 3.6 family members found with the same mutation.
Doel van het onderzoek
By performing a low-dose CT in patients with primary spontaneous pneumothorax (PSP) the typical pulmonary abnormalities, related to the mutation in FLCN, are detected. Patients will be tested for the FLCN mutation by performing a blood sample for analysis. By this method the Birt-Hogg-Dubé-syndrome syndrome can be detected and through that the carrier and affected relatives can be screened yearly for possible presence of renal cell carcinoma at an early stage.
Onderzoeksopzet
4 year
Onderzoeksproduct en/of interventie
lab, CT, questionnaire
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- Able to give written informed consent prior to participation in the study. Subjects must be able to read, comprehend and write at a level sufficient to complete study related materials.
- Subjects must have a diagnosis of spontaneous pneumothorax (this might be a 2nd PSP if not proven to be related to a known disease or the first contralateral pneumothorax)
- Age: at least 16 years of age at visit 1
- Sex: male or female
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
- Age under 16
- Subjects with claustrophobia making it impossible to perform a CT scan
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or it is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- A CT scan of the thorax is already been performed within a year before the PSP
- lung carcinoma
- lung metastases
- Iatrogenic pneumothorax
- secondary spontaneous pneumothorax
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
Toelichting
Each subject will be assigned a subject number at the time the informed consent is signed. Data will be pseudonymised.
Data will be accessible for the principal investigator, members of the study team, monitor and IGJ. Following closure of the study, all study records will be maintained for 15 years in a safe and secure location (Iron Mountain, Alphen a/d Rijn), as local regulations require.
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
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Andere (mogelijk minder actuele) registraties in dit register
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL7953 |
| Ander register | METC Leiden, Den Haag, Delft : METC NL 6812505819 |