Background Hereditary haemorrhagic telangiectasia (HHT) is an inherited disease of the vasculature presenting with nosebleeds, telangiectasia and arteriovenous malformations (AVMs). HHT is caused by gene mutations affecting the transforming growth factor beta (TGF-β) superfamily signalling pathway. As TGF-β signalling is crucial for embryonic lung maturation, respiratory homeostasis and plays a pivotal role in the pathogenesis of several respiratory diseases, we hypothesised that HHT could alter the respiratory environment and respiratory disease susceptibility. As a first step, we aimed to examine associations between HHT and other respiratory conditions common in the British population.
Methods An online questionnaire at www.imperial.ac.uk/medicine/HHTsurvey2012 was used to collect data. Questions regarding HHT were used to assign HHT status. Participants were categorised based on self-reported status, positive/negative family history and presence of Curaçao criteria (nosebleeds, telangiectasia in specific patterns, and AVMs) Participants’ demographics and coexisting respiratory conditions were analysed with Spearman’s, Mann-Whitney, and logistic regression analyses using STATA (version 12, Texas USA).
Results By data download on 5 April 2013, 1,465 participants had completed the questionnaire. 1,080 were classified as HHT patients and 179 as controls. Ages ranged from 17–92 (53)years. A history of smoking was provided by 31.5% of the HHT population and 33.1% of the controls. In univariate analyses, COPD, venous thromboemboli, pulmonary hypertension and sleep apnoea were more common in the HHT population in comparison to the controls (respectively, p = 0.038; p = 0.019; p = 0.004; p = 0.015). When multiple regression analyses were used to correct for age and smoking, the association with COPD was lost. However, the positive associations with pulmonary hypertension (p = 0.034), venous thromboemboli (p = 0.036) and sleep apnoea (p = 0.033) remained. Sleep apnoea demonstrated a 2.6 fold higher prevalence in the study HHT population (69/100,000) in comparison to published figures for the general population (27/100,000 from the Hospital Episodes System (HES).
Conclusions The study identified two known associations (HHT and pulmonary hypertension; HHT and venous thromboemboli), supporting the validity of the study methodology. Further investigation is needed to validate and understand the rationale for a possible novel association between HHT and sleep apnoea.
Lung and Asthma Information Agency. Obstructive Sleep Apnoea. Available at http://www.laia.ac.uk/pdfs/osa.pdf