The timing of intravenous antibiotics and clinical outcomes of Mycobacterium abscessus complex lung diseases.

BACKGROUND: The importance of early intravenous (IV) antibiotic use for Mycobacterium abscessus complex lung diseases (MABC-LD) treatment remains unknown. METHODS: A retrospective multi-centre observational study was conducted in Taiwan. Patients who were diagnosed with and received treatment for MABC-LD from January 2007 to April 2021 were included. Treatment outcome was defined as modified microbiological cure of MABC-LD.RESULTS: Of the 89 enrolled patients, 34 (38.2%) received IV antibiotics as part of the treatment regimen. The median time to IV initiation was 1 day (IQR 1???49); 24 (70.6%) of these patients received IV agents within 4 weeks, defined as early-use. Forty-two (47.2%) patients achieved modified microbiological cure. In the multivariable logistic analysis, early IV antibiotic use was an independent factor associated with modified microbiological cure (aOR 5.32, 95% CI 1.66???17.00), whereas high radiological score (aOR 0.86, 95% CI 0.73???1.00) demonstrated negative association.CONCLUSIONS: In the present study, early use of effective IV antibiotic was prescribed in a low percentage (27%) for MABC-LD. By contrast, early IV antibiotic use was correlated with higher microbiological cure than were late or non-use. Future larger and prospective studies are needed to validate the association.

Impact of comorbidities on survival following major injury across different types of road users.

BACKGROUND: While comorbidities and types of road users are known to influence survival in people hospitalised with injury, few studies have examined the association between comorbidities and survival in people injured in road traffic crashes. Further, few studies have examined outcomes across different types of road users with different types of pre-existing comorbidities. This study aims to examine differences in survival within 30 days of admission among different road user types with and without different pre-existing comorbidities. METHOD: Retrospective cohort study using data for all major road trauma cases were extracted from the NSW Trauma Registry Minimum Dataset (1 January 2013 - 31 July 2019) and linked to the NSW Admitted Patient Data Collection, and the NSW Registry of Births, Deaths and Marriages - death dataset. Pre-existing comorbidities and road user types were identified by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and Charlson Comorbidity Index in the Trauma Registry, hospital admission, and death datasets. Logistic regression was used to assess the associations between six types of road users (pedestrian, pedal cycle, two- and three-wheel motorcycle, car and pick-up truck, heavy vehicle and bus, and other types of vehicle) and death within 30 days of hospital admission while controlling for comorbidities. All models used 'car and pick-up truck driver/passenger' as the road user reference group and adjusted for demographic variables, injury severity, and level of impaired consciousness. RESULTS: Within 6253 traffic injury person-records (all aged ≥15 years old, ISS>12), and in final models, injured road users with major trauma who had a history of cardiovascular diseases (including stroke), diabetes mellitus, and higher Charlson Comorbidity Index score, were more likely to die, than those without pre-existing comorbidities. Furthermore, in final models, pedestrians were more likely to die than car occupants (OR: 1.68 - 1.77, 95CI%: 1.26 - 2.29 depending on comorbidity type). CONCLUSIONS: This study highlights the need to prioritize enhanced management of trauma patients with comorbidities, given the increasing prevalence of chronic medical conditions globally, together with actions to prevent pedestrian crashes in strategies to reach Vision Zero.

Does social support predict increased use of dental services in older men?

BACKGROUND: Past research on social support and dental visits in older people has been limited by cross-sectional design, limited social support dimensions and non-representative samples. METHODS: Data came from men with natural teeth completing Waves 3 and 4 of the Concord Health and Ageing in Men Project in Sydney, Australia. The relationship between social support at Wave 3 (2011-2012) and at least one dental visit per year at Wave 4 (2014-2016) was examined by Poisson regression. Social support was measured by structural (marital status, living arrangements, family support and social interaction) and functional (social support satisfaction) domains. RESULTS: About 673 men were analysed. Structural and functional social support were not associated with the pattern of usual dental visits 5 years later in univariable or multivariable analyses. The only consistent significant factor was income source, with older men who had other sources of income more likely to regularly visit the dentist than older men solely reliant on the pension for income (prevalence ratio: 1.31, 95% CI: 1.13-1.52). CONCLUSIONS: We found no differences in the pattern of usual dental visits between older men with different levels and types of social support. For older Australian men, income source seems to be the most important determinant of regular dental visits. © 2022 Australian Dental Association.

Impact of different subspecies on disease progression in initially untreated patients with Mycobacterium avium complex lung disease.

OBJECTIVE: Disease progression is a strong indicator of treatment for Mycobacterium avium complex lung disease (MAC-LD). The impact of MAC subspecies on the risk of disease progression remains uncertain in MAC-LD patients. METHODS: In this cohort study, we included MAC-LD patients from 2013 to 2018 and classified them into M. intracellulare, M. avium, M. chimaera and other subspecies groups by genotype. We observed the disease progression of MAC-LD, indicated by antibiotic initiation and/or radiographic progression. We used Cox regression analysis to assess predictors for disease progression. RESULTS: Of 105 MAC isolates from unique MAC-LD patients, 35 (33%) were M. intracellulare, 41 (39%) M. avium, 16 (15%) M. chimaera and 13 (12%) other subspecies. After a mean follow-up time of 1.3 years, 56 (53%) patients developed disease progression: 71% (25/35), 54% (22/41), 31% (4/13) and 31% (5/16) in patients with M. intracellulare, M. avium, others and M. chimaera, respectively. The independent predictors for disease progression were M. chimaera subspecies (HR 0.356, 95% CI (0.134-0.943)), compared with the reference group of M. intracellulare, body mass index ≤20 kg/m2 (HR 1.788 (1.022-3.130)) and initial fibrocavitary pattern (HR 2.840 (1.190-6.777)) after adjustment for age, sex and sputum smear positivity. Among patients without fibrocavitary lesions (n = 94), the risk of disease progression significantly decreased in patients with other subspecies (HR 0.217 (0.050-0.945)) and remained low in those with M. chimaera (HR 0.352 (0.131-0.947)). CONCLUSIONS: Mycobacterium chimaera was not uncommon in this study; unlike M. intracellulare, it was negatively correlated with disease progression of MAC-LD, suggesting a role of MAC subspecies identification in prioritizing patients.

Progression of chronic kidney disease and the risk of tuberculosis: an observational cohort study.

Little is known about tuberculosis (TB) risk in the earlier stages of chronic kidney disease (CKD). To investigate the relationship between CKD at all stages and the risk of incident TB. We conducted a cohort study using 100 058 participants of a community-based health screening programme in northern Taiwan, 2005-2008. Renal function was ascertained at baseline using serum creatinine level and the urine dipstick test. The occurrence of active TB was ascertained using the National Tuberculosis Registry. Cox proportional hazards regression was used to estimate the association between CKD and TB. During a median follow-up of 7.5 years, TB incidence was 472. In the Cox regression analyses, individuals with Stage 1-4 CKD had a 25% increase in TB hazard than those without disease (adjusted hazard ratio [aHR] 1.25, 95%CI 1.02-1.54). A positive correlation between CKD stage and TB was observed (P = 0.02 for trend). TB risk increased by 5.1% with every 10 ml/min/1.73 m² decrease in the estimated glomerular filtration rate (aHR 1.05, 95%CI 0.99-1.12). Our results suggested an increased risk of TB in early-stage CKD. TB prevention efforts should consider individuals with earlier stages of CKD. .

Oral health behaviours of older Australian men: the Concord Health and Ageing in Men Project.

BACKGROUND: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of older Australian men. The aim of this paper is to describe the oral health behaviours and dental service use of CHAMP participants and explore associations between oral health behaviours with and general health status. METHOD: Information collected related to socio-demographics, general health, oral health service-use and oral health behaviours. Key general health conditions were ascertained from the health questionnaire and included physical capacity and cognitive status. RESULTS: Fifty-seven percent of the men reported visiting a dental provider at least once or more a year and 56.7% did so for a "dental check-up". Of those with some natural teeth, 59.3% claimed to brush their teeth at least twice or more a day. Most men (96%) used a standard fluoride toothpaste. Few participants used dental floss, tooth picks or mouth-rinses to supplement oral hygiene. Cognitive status and self-rated general health were associated with dental visiting patterns and toothbrushing behaviour. CONCLUSIONS: Most older men in CHAMP perform favourable oral health behaviours. Smoking behaviour is associated with less favourable dental visiting patterns, and cognitive status with toothbrushing behaviour.

Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc.

The aim of this study was to immunolocalise type VI collagen and perlecan and determine their interactive properties in the intervertebral disc (IVD). Confocal laser scanning microscopy co-localised perlecan with type VI collagen as pericellular components of IVD cells and translamellar cross-bridges in ovine and murine IVDs. These cross-bridges were significantly less abundant in the heparin sulphate deficient Hspg2 exon 3 null mouse IVD than in wild type. This association of type VI collagen with elastic components provides clues as to its roles in conveying elastic recoil properties to annular tissues. Perlecan and type VI collagen were highly interactive in plasmon resonance studies. Pericellular colocalisation of perlecan and type VI collagen provides matrix stabilisation and cell-matrix communication which allows IVD cells to perceive and respond to perturbations in their biomechanical microenvironment. Perlecan, at the cell surface, provides an adhesive interface between the cell and its surrounding extracellular matrix. Elastic microfibrillar structures regulate tensional connective tissue development and function. The 2010 Global Burden of Disease study examined 291 disorders and identified disc degeneration and associated low back pain as the leading global musculoskeletal disorder emphasising its massive socioeconomic impact and the need for more effective treatment strategies. A greater understanding of how the IVD achieves its unique biomechanical functional properties is of great importance in the development of such therapeutic measures.

Factors associated with subsequent nontuberculous mycobacterial lung disease in patients with a single sputum isolate on initial examination.

Very few studies have focused on the outcome and management of patients with a single sputum isolate of nontuberculous mycobacterium (NTM) on initial examination. Patients with a single isolate of Mycobacterium avium complex (MAC), M. chelonae-abscessus, M. kansasii, or M. fortuitum from at least three sputum samples collected within 1 month were retrospectively identified. Those with follow-up sputum samples within 1 year were included in the analysis. Among the 202 patients included, M. fortuitum (n = 71, 35.1%) and MAC (n = 70, 34.7%) were the most common NTM species isolated, followed by M. chelonae-abscessus (n = 40, 19.8%) and M. kansasii (n = 21, 10.4%). The mean clinical follow-up period was 26.2 months. Forty-four patients (21.8%) had subsequent positive cultures of the same NTM species, while eight (4.0%) had bronchiectasis and developed NTM lung disease (NTM-LD). Neither patients without bronchiectasis nor those with M. fortuitum subsequently developed NTM lung disease. Among bronchiectatic patients with NTM other than M. fortuitum, age ≤65 years (p 0.006, OR 32.13), malignancy (p 0.048, OR 14.35), and initial radiographic score >2 (p 0.027, OR 20.06) were associated with subsequent NTM-LD. In all of the NTM patients, bronchiectasis (p <0.001, OR 5.46) and age ≤65 years (p 0.002, OR 3.29) were significantly associated with subsequent positive NTM culture. In patients with a single isolation of NTM from respiratory specimens, the presence of bronchiectasis and younger age indicates higher risk of subsequent culture-positivity and NTM-LD. Single isolation of M. fortuitum is of little clinical significance. Other patients with NTM, younger age, and more severe radiographic pulmonary lesion also warrant further attention.

A review of models relevant to road safety.

It is estimated that more than 1.2 million people die worldwide as a result of road traffic crashes and some 50 million are injured per annum. At present some Western countries' road safety strategies and countermeasures claim to have developed into 'Safe Systems' models to address the effects of road related crashes. Well-constructed models encourage effective strategies to improve road safety. This review aimed to identify and summarise concise descriptions, or 'models' of safety. The review covers information from a wide variety of fields and contexts including transport, occupational safety, food industry, education, construction and health. The information from 2620 candidate references were selected and summarised in 121 examples of different types of model and contents. The language of safety models and systems was found to be inconsistent. Each model provided additional information regarding style, purpose, complexity and diversity. In total, seven types of models were identified. The categorisation of models was done on a high level with a variation of details in each group and without a complete, simple and rational description. The models identified in this review are likely to be adaptable to road safety and some of them have previously been used. None of systems theory, safety management systems, the risk management approach, or safety culture was commonly or thoroughly applied to road safety. It is concluded that these approaches have the potential to reduce road trauma.

Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan.

BACKGROUND: Obstructive uropathy and chronic urinary tract infection increase the risk of urinary tract cancer. Urinary tuberculosis (UTB) can cause chronic urinary tract inflammation, lead to obstructive uropathy, and potentially contribute to the development of urinary tract cancer. However, the association between UTB and urinary tract cancer has not been studied. METHODS: This study enrolled 135 142 tuberculosis (TB) cases (male, 69%) from a nationwide health insurance research database in Taiwan and investigated the risk factors for urinary tract cancer, with emphasis on a history of UTB. The incidence of urinary tract cancer in the general population without TB was also calculated for comparison. RESULTS: The TB patients had a mean age of 57.5 ± 19.5 years. Of the 1287 UTB and 133 855 non-UTB patients, 15 (1.2%) and 396 (0.3%) developed urothelial carcinoma, respectively (P<0.001); and 2 (0.2%) and 96 (0.1%) developed renal cell carcinoma, respectively (P=0.240). Cox regression analysis revealed that age, male sex, end-stage renal disease, obstructive uropathy, arsenic intoxication, organ transplantation, and UTB (hazard ratio: 3.38 (2.01-5.69)) were independent risk factors for urothelial carcinoma. The hazard ratio of UTB was higher among female patients (5.26 (2.12-13.06)) than that among male patients (2.96 (1.57-5.60)). CONCLUSION: Urinary tuberculosis had a strong association with urothelial carcinoma, but not with renal cell carcinoma. In TB endemic areas, the urinary tract of TB patients should be scrutinised. It is also imperative that these patients be followed-up carefully in the post-treatment period, and urinalysis, ultrasonography or endoscopy should be an integral part of the follow-up.

Hepatotoxicity due to first-line anti-tuberculosis drugs: a five-year experience in a Taiwan medical centre.

BACKGROUND: Hepatotoxicity with first-line drugs, a major complication of anti-tuberculosis treatment, has not been studied by time-dependent analysis. DESIGN: Adult patients diagnosed with pulmonary tuberculosis (PTB) from 2005 to 2009 were reviewed retrospectively. Hepatotoxicity during anti-tuberculosis treatment was defined by symptomatic elevation of liver transaminases ≥3 times the upper limit of normal, or ≥5 times if asymptomatic. Risk factors for hepatotoxicity were investigated using time-dependent Cox regression analysis. RESULTS: Of 926 patients identified and followed for 4122.9 person-months (pm), 111 (12.0%) developed hepatotoxicity after a median 38.0 days from start of treatment. Around 3.5% had severe hepatotoxicity. The most common symptoms were general malaise and poor appetite. The incidence rate of hepatotoxicity was 0.59, 0.69 and 3.71/100 pm for isoniazid, rifampicin (RMP) and pyrazinamide (PZA), respectively. Old age, female sex, autoimmune disease, human immunodeficiency virus infection, more days with PZA in the last 8-14 days, and fewer days with RMP in the last 15-21 days before hepatotoxicity were independent risk factors for hepatotoxicity during treatment. CONCLUSION: A significant number of adult patients on first-line treatment experience hepatotoxicity. PZA is the most common causative drug. For high-risk patients, careful adjustment of the anti-tuberculosis regimen and regular monitoring of liver transaminases are necessary.

Expression of toll-like receptor 2 and plasma level of interleukin-10 are associated with outcome in tuberculosis.

Toll-like receptor (TLR) 2-mediated innate immunity is an important defense system against Mycobacterium tuberculosis infection. Studies on TLR2 protein expression and downstream cytokines in tuberculosis patients are lacking. TLR2 expression in the peripheral blood monocytes of 87 tuberculosis patients and 94 healthy subjects was evaluated using flow cytometry. TLR2 expression and its downstream cytokines, including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon-gamma, were correlated with the clinical manifestations and outcomes of tuberculosis. The TLR2 expression in peripheral blood monocytes was higher in tuberculosis patients than in healthy subjects. Among the tuberculosis patients, those aged ≥70 years with disseminated tuberculosis or aged <70 years with symptom duration ≥14 days had lower initial TLR2 expression. After two months of treatment, TLR2 expression decreased in most patients, except in those whose sputum samples remained culture-positive for M. tuberculosis. Proportional hazards regression analyses revealed that high initial TLR2 expression and IL-10 plasma level were associated with shorter survival. TLR2 may play an important role in the course of tuberculosis. Its expression on peripheral blood monocytes and the plasma level of the downstream anti-inflammatory cytokine IL-10 may be important outcome predictors and have potential use in the management of tuberculosis patients.

Mycobacterial peritonitis: difference between non-tuberculous mycobacteria and Mycobacterium tuberculosis.

Unlike tuberculous peritonitis, peritonitis due to non-tuberculous mycobacteria (NTM) has unclear clinical manifestations. This study aimed to clarify the clinical manifestations and laboratory results of NTM peritonitis and compare it to tuberculous peritonitis. This retrospective study was conducted from 2000 to 2008 in a medical centre in Taiwan. Patients with mycobacteria isolated from ascites were identified and compared according to causative pathogens (Mycobacterium tuberculosis or NTM). Those with NTM peritonitis were further classified into the 'probable' and 'possible' groups based on diagnostic evidence. Twenty-five patients with NTM peritonitis and 65 with tuberculous peritonitis were reviewed. Mycobacterium avium complex was the most common NTM pathogen (52%). There was no obvious difference between the 'probable' and 'possible' NTM peritonitis groups regarding age and laboratory data. Patients with NTM peritonitis and those with tuberculous peritonitis had no differences in age or gender but varied in symptoms and serum laboratory data. NTM peritonitis was 100% associated with underlying co-morbidities and had lower proportions of lymphocytes and albumin level in ascites. Twelve (48%) NTM peritonitis and 21 (32%) tuberculous peritonitis patients died during the 6-month follow-up. Anti-mycobacterial treatment, but not mycobacterial species, was correlated with better 6-month survival. In Taiwan, NTM is responsible for 28% of mycobacterial peritonitis cases, which have a poor prognosis if untreated. There are some differences in clinical manifestations between NTM and tuberculous peritonitis. NTM peritonitis should be considered in patients with peritonitis but without causative microorganisms identified other than NTM.

Risk factors for 30-day readmission in general medical patients admitted from the emergency department: a single centre study.

BACKGROUND: Overcrowding in emergency departments (ED) around the world is an increasingly serious problem with an adverse impact on both patient flow and patient outcomes. A significant contributing factor to ED overcrowding is possibly due to readmission. Risk factors for readmission in patients admitted from ED are rarely studied, particularly in Asian countries where the length of stay is reportedly longer. METHODS: A retrospective study of patients admitted to general medical wards from the ED of a referral centre in northern Taiwan from November 2009 to April 2010 was conducted. The primary outcome was 30-day hospital readmission and clinical characteristics were analysed for predictors of readmission. RESULTS: Of the recruited 2698 patients, 451 (16.7%) were readmitted within 30 days after discharge. Age, gender, marital status and the activities of daily living (Barthel's score) were not associated with 30-day readmission. Higher Charlson score ((score 2-4) hazard ratio (HR): 1.42, 95% confidence interval (CI): 1.07-1.89; (score >4) HR: 1.93, 95% CI: 1.37-2.73), longer hospital stay ((8-14 days) HR: 1.51, 95% CI: 1.17-1.95; (15-28 days) HR: 1.64, 95% CI: 1.22-2.19; (>28 days) HR: 1.97, 95% CI: 1.43-2.71), and presence of underlying active malignancy (HR: 1.66, 95% CI: 1.27-2.16) and anaemia (HR: 1.26, 95% CI: 1.02-1.55) were independently associated with readmission. CONCLUSION: Medical patients admitted from the ED of a referral centre have a 30-day readmission rate of 16.7%. Post-discharge care should focus on patients with higher Charlson score, longer hospitalisation, anaemia and underlying active malignancy, which are independent predictive factors for 30-day readmission.

Use of soluble triggering receptor expressed on myeloid cells-1 in non-tuberculous mycobacterial lung disease.

BACKGROUND: Serum biomarkers are rarely studied in patients with non-tuberculous mycobacterial lung disease (NTM-LD). OBJECTIVE: To investigate the role of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory markers in NTM-LD. DESIGN: From April 2009 to March 2010, patients with NTM culture-positive respiratory specimens who were clinically and radiographically suspected of NTM-LD were evaluated for serum levels of sTREM-1, C-reactive protein, procalcitonin and interferon-gamma. RESULTS: Of the 86 patients enrolled, 60 fulfilled the diagnosis of NTM-LD. Using the receiver-operating characteristics curve analysis, serum sTREM-1 had the highest discriminative power for NTM-LD and colonisation (area under the curve = 0.714). Using a cut-off value of 180 pg/ml, the sensitivity and specificity of sTREM-1 were respectively 58% and 89%. Logistic regression analysis revealed that Mycobacterium avium complex, M. kansasii, positive sputum acid-fast smear and higher serum sTREM-1 level were independent risk factors for NTM-LD. Age >65 years and higher serum sTREM-1 level were associated with worse 6-month survival. CONCLUSION: In patients with respiratory specimens that are culture-positive for NTM with clinical suspicion of NTM-LD, serum sTREM-1 level measurements may be helpful in diagnosing and predicting outcome for NTM-LD.

Non-tuberculous mycobacterial pleurisy: an 8-year single-centre experience in Taiwan.

OBJECTIVE: To investigate the clinical characteristics and outcomes of patients with pleurisy due to non-tuberculous mycobacteria (NTM), which are currently unclear. DESIGN: From 2000 to 2007, patients with NTM and Mycobacterium tuberculosis isolated from pleural effusion (PE) samples were identified and compared. RESULTS: Thirty-five NTM patients and 140 tuberculosis (TB) patients were reviewed. Patients with NTM pleurisy were less likely to have lung involvement and receive anti-mycobacterial treatment compared with those with tuberculous pleurisy. NTM pleurisy had a higher PE leukocyte count and a lower percentage of lymphocytes. M. avium complex (MAC) was the most common pathogen in NTM pleurisy. Patients with MAC pleurisy were younger and tended to have more extra-pleural involvement and immune dysfunction. One-year mortality in the NTM pleurisy group was 37%, and anti-NTM treatment was associated with better survival. Patients with additional diagnostic evidence were more likely to receive anti-NTM treatment. CONCLUSION: NTM pleurisy is common and has a high 1-year mortality rate. Anti-NTM treatment may provide better 1-year survival and should be considered once NTM pleurisy is diagnosed.

The role of chest radiography in the suspicion for and diagnosis of pulmonary tuberculosis in intensive care units.

BACKGROUND: The role of chest radiography (CXR) in the clinical diagnosis and suspicion of pulmonary tuberculosis (PTB) remains uncertain in the intensive care unit (ICU) setting. DESIGN: This case-control study compared the radiographic findings between ICU patients with and without co-existing PTB to define any predictive patterns for the diagnosis of PTB. Further analysis aimed to elucidate the impact of CXR on the clinical suspicion of PTB. RESULTS: Eighty-nine (89) patients with PTB and an equal number of matched controls were evaluated. Consolidation was the most frequent radiographic pattern. There were no specific predictors for diagnosing PTB in the ICU. Of 89 patients, 55 (62.9%) had a delay in clinical suspicion of PTB. The time from ICU admission to TB diagnosis was significantly delayed in the group without clinical suspicion (30.7 vs. 5.3 days, P < 0.001). In multivariate analysis, a history of PTB was significantly associated with the clinical suspicion of PTB (OR 7.94, P = 0.012), but CXR patterns were not. CONCLUSION: CXR does not contribute as much as expected in the clinical diagnosis and suspicion of PTB in the ICU setting.

Effect of active and passive cigarette smoking on CYP1A2-mediated phenacetin disposition in Chinese subjects.

The effect of active and passive cigarette smoking on CYP1A2-mediated phenacetin disposition was evaluated in a controlled study of 36 healthy Chinese subjects. Each subject was administered a single oral dose of phenacetin (900 mg), and frequent blood samples were taken for up to 12 hours for simultaneous high-pressure liquid chromatography determinations of plasma concentrations of phenacetin and metabolically derived paracetamol. Compared with values observed in controls not exposed to cigarette smoking, subjects who smoked 7 to 40 (median, 20) cigarettes per day exhibited a 2.5-fold higher phenacetin apparent oral clearance (7.2, 4.3-12.0 L x h(-1) x kg(-1) vs 2.9, 1.8-4.6 L x h(-1) x kg(-1) [geometric means, 95% confidence intervals]; n = 12, p < 0.05). In subjects exposed to passive smoking, phenacetin's apparent oral clearance (3.6, 2.0-46.6 L x h(-1) x kg(-1), n = 12) was intermediate between the values observed in the two other groups. Plasma paracetamol levels were moderately lower in active smokers than in passive smokers and controls. These results demonstrated that, in contrast to results found in previous studies, Chinese subjects were fully susceptible to the inducing effect of cigarette smoke on CYP1A2 activity.