Predictors of non-cystic fibrosis bronchiectasis in Indigenous adult residents of central Australia: results of a case–control study

Abstract

The human T-cell leukaemia virus type 1 (HTLV-1) is associated with pulmonary inflammation. Indigenous Australians in central Australia have a very high prevalence of HTLV-1 infection and we hypothesised that this might contribute to high rates of bronchiectasis in this population.80 Indigenous adults with confirmed bronchiectasis, each matched by age, sex and language to two controls without bronchiectasis, were recruited. Case notes and chest imaging were reviewed, HTLV-1 serology and the number of peripheral blood leukocytes (PBLs) infected with HTLV-1 ( pro-viral load (PVL)) were determined, and radiological abnormality scores were calculated. Participants were followed for a mean±SD of 1.14±0.86 years and causes of death were determined.Median (interquartile range) HTLV-1 PVL for cases was 8-fold higher than controls (cases 213.8 (19.7-3776.3) copies per 10 5 PBLs versus controls 26.6 (0.9-361) copies per 10 5 PBLs; p=0.002). Radiological abnormality scores were higher for cases with HTLV-1 PVL ⩾1000 copies per 10 5 PBLs and no cause of bronchiectasis other than HTLV-1 infection. Major predictors of bronchiectasis were prior severe lower respiratory tract infection (adjusted OR (aOR) 17.83, 95% CI 4.51-70.49; p<0.001) and an HTLV-1 PVL ⩾1000 copies per 10 5 PBLs (aOR 12.41, 95% CI 3.84-40.15; p<0.001). Bronchiectasis (aOR 4.27, 95% CI 2.04-8.94; p<0.001) and HTLV-1 PVL ⩾1000 copies per 10 5 PBLs (aOR 3.69, 95% CI 1.11-12.27; p=0.033) predicted death.High HTLV-1 PVLs are associated with bronchiectasis and with more extensive radiological abnormalities, which may result from HTLV-1-mediated airway inflammation.@ERSpublications Higher numbers of HTLV-1-infected cells in peripheral blood are associated with bronchiectasis and more extensive radiological abnormalities among those with no cause for bronchiectasis other than HTLV-1 infection

Very high prevalence of infection with the human T cell leukaemia virus type 1c in remote Australian Aboriginal communities: Results of a large cross-sectional community survey

“…The study also systematically measured HTLV-1 PVL in study participants, extending previously published observations from these communities [ 11 ] to reveal a wide range of inter-individual HTLV-1 proviral loads, exceeding 1000 copies per 10 5 PBL for 36% of participants with HTLV-1. An HTLV-1 PVL exceeding this level has been associated with serious adverse outcomes, including bronchiectasis and death, in hospital-based studies in this population [ 25 , 26 ]. A strong association between high HTLV-1 PVL and chronic pulmonary disease was also found among 415 adult residents of these communities who were examined by a physician blinded to HTLV-1 status [ 11 ].…”

“…HTLV-1 PVL data are therefore presented relative to the number of peripheral blood leukocytes and our data cannot be compared to that from other studies that have used peripheral blood mononuclear cells as their reference. Nevertheless, our methods have strong internal validity that has allowed clinically meaningful comparisons between symptomatic and asymptomatic participants in previous studies [ 11 , 25 , 26 ].…”

“…Each of the recognised complications of HTLV-1 has been described in central Australia [ 14 ]. Infection with HTLV-1 is also associated with an increased risk of death in all endemic areas where mortality has been studied [ 52 ], and a higher HTLV-1 PVL predicts death at ASH [ 25 , 26 ].…”

Molecular Biology and Diversification of Human Retroviruses

“…HTLV-1 is also associated with a number of other inflammatory disorders, including bronchiectasis. A recent study found that in Indigenous adults in central Australia, HTLV-1 proviral loads are 8-fold higher in patients with bronchiectasis compared with healthy controls, and patients with an HTLV-1 proviral load greater than 1000 copies per 100,000 peripheral blood leukocytes were over 12-times more likely to develop bronchiectasis (37).…”

An Overview of Human T-Lymphotropic Virus Type 1 Lung Injury

“…The studies about HTLV-1 related lung diseases shows that these abnormal CT findings are more common in TSP-HAM individuals than asymptomatic carriers (16,17,23), their higher frequency of lung injury can be explained by their major in situ inflammatory processes (8,17,24,25,27) and is associated with high HTLV-1 proviral load (37,38). These individuals also exhibit three or more lesions types, and a combination between bronchiectasis and other lesions in HRCT, such as pleural thickening, parenchymal bands, interlobular septum thickening, centrilobular nodules, and parenchymal bands (17).…”