detailed clinical and social data were collected by case managers for all tb patients undergoing treatment in london on july 1 , 2003 . analyses were restricted to pulmonary patients 1560 years of age ( n = 970 ) . we used univariate analyses to compare the characteristics of crack cocaine users , other hard - drug users ( predominantly heroin users but excluding those who used only alcohol and marijuana ) , and those not known to use drugs . a separate category was included for hard - drug users not known to use crack cocaine to have a group with comparable levels of social deprivation , addiction related problems , and difficulty in accessing health services . to test the hypothesis that smear positivity at diagnosis was associated with crack cocaine use , we used a multivariate model with backwards elimination to exclude variables that did not make a significant contribution to the model . variables initially included are shown in table 1 ; the final model is shown in table 2 . * tb , tuberculosis ; ed , emergency department ; mdr , multidrug resistant ; inh , isoniazid ; dot , directly observed therapy . * or , odds ratio ; ci , confidence interval ; inh , isoniazid resistant ; mdr , multidrug - resistant ; ed , emergency department . drug users to have been born in the united kingdom , of white or black caribbean ethnic origin , homeless , alcohol abusers , or have a history of imprisonment . non  crack drug users tended to have the longest delays between diagnosis and treatment and crack users the shortest , but this tendency did not reach significance ( table 1 ) . crack cocaine users were statistically significantly more likely to seek treatment at emergency departments , to adhere poorly to treatment regimen , or default from treatment altogether . drug users were also more likely to have isoniazid - resistant disease . among crack cocaine users this was primarily related to a large outbreak of isoniazid - resistant tb ( 11 ) . among crack cocaine users , diagnosis showed that 86% were smear positive compared with 36% of patients not known to use drugs ( relative risk [ rr ] 2.4 , 95% confidence interval [ ci ] 2.02.9 ) , p<0.001 ) and 59% of drug users not known to use crack cocaine ( rr 1.6 , 95% ci 1.42.0 , p<0.001 ) . multivariate analysis showed that the risk for smear - positive disease was higher for drug users than for those not known to use drugs ( odds ratio [ or ] 1.9 , 95% ci 1.23.0 , p = 0.007 ) and highest in crack cocaine users ( or 6.6 , 95% ci 1.824.3 , p = 0.005 ) . other significant risk factors for smear positivity were being of black caribbean ethnicity , having multidrug - resistant disease , and seeking treatment at an emergency department . when the multivariate model was restricted to include only hard - drug users , crack cocaine users were still significantly more likely than other drug users to be smear positive ( p = 0.02 ) . smear - positive disease is 2.4 times more likely to be diagnosed in crack cocaine users than in non  drug users , whereas hard - drug users not known to use crack cocaine are 1.6 times more likely to be diagnosed with smear - positive disease . crack cocaine users were significantly more likely than other drug users to be smear positive on diagnosis . the increased risk for smear - positive disease in crack cocaine users was not due to diagnostic delays . hard - drug users who were not confirmed as crack cocaine users had the longest diagnostic delays . crack cocaine users had the shortest diagnostic delays , potentially attributable to rapidly progressive , debilitating disease . crack cocaine users were also more likely to seek treatment at an emergency department rather than primary care services . again , the choice of healthcare service may be related to the severity of disease . we included non  crack drug users as a comparison group because they have a similar social profile and similar access to healthcare . therefore , we are confident that the extremely high levels of smear positivity on diagnosis in crack cocaine users are not due to a long duration of clinical illness preceding diagnosis . in the multivariate model , crack cocaine use remains strongly associated with smear - positive disease after controlling for a wide variety of other potential confounders . other risk factors include ethnicity ( drug use was common among black carribean patients and may have been underreported ) ; treatment at an emergency department ( possibly a marker of disease severity ) ; and multidrug - resistant disease . we are uncertain why multidrug - resistant cases were more likely to be smear - positive on diagnosis ; however , previous studies have found that cavitary disease is a risk factor for drug resistance ( 12 ) . the fact that smear positivity was significantly more prevalent in patients known to use crack cocaine when compared with other hard - drug users suggests that this additional risk may be attributable to a biological component . plausible biological mechanisms to explain the increased risk of smear - positive disease include poor alveolar macrophage antimicrobial activity in crack cocaine users due to decreased inducible nitric oxide synthase activity ( 13 ) and direct effects on the lung ( 10 ) . it is likely that a proportion of hard - drug users were incorrectly classified as not using crack cocaine due to nondisclosure . this would reduce the apparent differences in levels of smear positivity between the groups . nevertheless , despite relatively small numbers of known crack cocaine users , there is a significantly ( p = 0.02 ) higher proportion of smear - positive disease in these patients compared with other hard - drug users . persons frequenting crack houses are likely to have multiple risk factors for active pulmonary tb . prolonged sharing of closed and confined airspace , intensive coughing , and other acute pulmonary complications of crack cocaine inhalation promote transmission . drug users are more likely than non  drug users to default treatment , to remain infectious for prolonged periods after diagnosis , and to acquire drug - resistant tb ( 15 ) . . users may experience addiction - related problems that complicate access to healthcare and aggravate transmission , possibly aggravated by a biological driver that may increase susceptibility to infection and progression to infectious disease . additional studies are needed to investigate the possible biological role of crack cocaine in the development of infectious forms of tb .