Inhaled corticosteroids and risk of tuberculosis in patients with obstructive lung diseases: A systematic review and meta-analysis of non-randomized studies

Background: An association between systemic corticosteroids and tuberculosis (TB) is reported in the literature. Here within, we conducted a systematic review and meta-analysis to evaluate the effects of inhaled corticosteroids (ICS) on the risk of TB in patients with obstructive lung diseases.Methods: The review was registered on PROSPERO (CRD42018095874). PubMed, CENTRAL, Scopus and Web of Science were searched from inception to September 2018. Papers reporting cases of incident TB in patients with obstructive lung diseases were included; studies without data on ICS use were excluded. Simultaneous use of oral corticosteroids (OCS) and population attributable fraction (PAF) for TB from ICS exposure were also assessed. Data were analyzed using a generic inverse variance method with a random-effects model. ORs with 95% CI were estimated.Results: Out of 4044 retrieved papers, 9 articles evaluating adult patients only were included in the review. 36,351 patients were prescribed ICS, while 147,171 were not. Any ICS use was associated with an increased risk of TB versus no ICS use (OR=1.46; 95% CI 1.06 to 2.01; p=0.02; I-2=96%). A similar result was also found for current ICS use versus prior/no ICS use, as well as for high, moderate and low ICS dose versus no ICS. When simultaneous OCS use was evaluated, the independent contribution of ICS was confirmed only in patients not on OCS (OR=1.63; 95% CI 1.05 to 2.52; p=0.03; I-2=94%). Only 0.49% of all TB cases could be attributable to ICS exposure.Conclusions: Despite the association between ICS and TB, the contribution of this risk factor to the epidemiology of TB seems to be limited. As a consequence, no population-based interventions are warranted. Rather, this risk should be taken into account on an individual basis, particularly in those patients with a high risk of progression from LTBI to TB.