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 10⁵ PBLs versus controls 26.6 (0.9-361) copies per 10⁵ PBLs; p=0.002). Radiological abnormality scores were higher for cases with HTLV-1 PVL ≥1000 copies per 10⁵ 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 10⁵ 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 10⁵ 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.

FIGURE 1

Recruitment flowchart for cases and matching to controls: recruitment was based on discharge diagnosis. Among 106 subjects with a discharge diagnosis of bronchiectasis, 104 were examined by chest high-resolution computed tomography (HRCT), which confirmed the diagnosis in 78 cases. Chest HRCT was not available for two cases for which diagnosis was confirmed by chest radiography findings of cystic bronchiectasis and by bronchography. Each case was then matched to two controls who were admitted during the study period with 1) no lower respiratory tract infection on admission, 2) no evidence of chronic lung disease on chest radiography and 3) no discharge diagnosis of either bronchiectasis or a human T-cell leukaemia virus type 1-associated disease. Reasons for admission of controls included: 1) surgical management n=121 (75.6%) (skin and soft tissue infections n=45, orthopaedic n=22, general surgical n=20, trauma n=27, pancreatitis n=3, burns n=3, tonsillectomy n=1), 2) medical reasons n=36 (22.5%) (heart disease n=11, renal disease n=8, neurological disease n=6, gastroenterological disorders n=4, diabetic ketoacidosis n=1, constipation n=2, pelvic inflammatory disease n=1, alcohol withdrawal n=1, malnutrition n=1, acute rheumatic fever n=1) and 3) to care for other patients n=3 (1.9%).

FIGURE 2

Dot plots with median (interquartile range (IQR)) comparing human T-cell leukaemia virus type 1 (HTLV-1) pro-viral load (PVL) for controls (n=53), cases with HTLV-1 and risk factors for bronchiectasis (n=10), and cases with no risk factors predisposing to bronchiectasis other than HTLV-1 infection (n=32). Risk factors for bronchiectasis included severe pneumonia (n=5), empyema (n=2), pulmonary abscess (n=1), pulmonary tuberculosis (n=1) and severe childhood bronchiolitis (n=1). Median (IQR) HTLV-1 PVLs for controls, cases with other risk factors and cases without risk factors were 3.28 (0.49–5.89), 6.01 (2.98–7.58) and 5.35 (3.01–8.32) log unit copies per 10⁵ peripheral blood leukocytes (PBLs), respectively. HTLV-1 PVLs were significantly higher for cases with (p=0.0178) and without (p=0.0108) risk factors for bronchiectasis when compared with controls (Mann–Whitney test). There was no difference in HTLV-1 PVLs between groups for cases.