Assessment and management of patients with chronic cough by Certified Respiratory Educators: a randomized controlled trial.

BACKGROUND: The value of other health care professionals is increasingly being recognized to compensate for the shortage of physicians in Canada. Chronic cough is one of the most common reasons for consultation with a respirologist. In the present study, a prospective, randomized, controlled study was undertaken to determine whether Certified Respiratory Educators (CREs) could manage screened patients with chronic cough as effectively as respirologists. METHODS: An eight-week, prospective, parallel-design, randomized, controlled trial of the management of chronic cough patients was conducted. Patients were screened to exclude those with potentially life-threatening conditions. The primary outcome was the number of patients whose cough resolved or subjectively improved. RESULTS: A total of 198 patients were randomly assigned, and eight-week data were available on 151 patients. Mean age of the patients was 49.8+/-13.4 years, 70.2% were female and median cough duration was 16 months. The screening process was effective and referral wait times decreased from a median of two months to less than four weeks (P<0.0001). The educators averaged 4.9 contacts per patient compared with 2.7 by the physicians over the eight-week study period (P<0.0001). Most patients had had multiple therapeutic trials before referral. Cough resolved or improved in two-thirds of the patients at eight weeks; however, more patients showed improvement in the educator arm than in the physician arm, P<0.02. Cough-specific quality of life improved similarly in the two study arms at eight weeks (physician arm: 61.5+/-14.1 to 52.6+/-14.4, P<0.0001; CRE arm: 58.1+/-14.9 to 50.0+/-15.8, P=0.0003). CONCLUSIONS: CREs can safely and effectively assess, as well as appropriately treat, screened patients with chronic cough with a resultant reduction in wait times.

Tuberculosis in Calgary, Canada, 1995-2002: site of disease and drug susceptibility.

SETTING: A centre managing all tuberculosis (TB) cases in the population of the Calgary region in Canada. OBJECTIVE: To facilitate the diagnosis and management of TB by examining the distribution of TB by site of disease and the prevalence and pattern of drug-resistant Mycobacterium tuberculosis in a north American setting. DESIGN: A retrospective analysis of data collected at the time of diagnosis of all TB cases recorded during the 8-year period 1995-2002. Data collected included demographic information, site of disease, method of diagnosis and M. tuberculosis drug susceptibility. RESULTS: During the 8-year period, 435 cases of TB were diagnosed: 49% had exclusively extra-pulmonary disease. Lymph node disease (usually cervical) accounted for 44% of the extra-pulmonary cases. A culture of M. tuberculosis resistant to at least one first-line anti-tuberculosis drug was detected in 16% of the initial isolates. All of the resistant strains were found in foreign-born patients and resistance was more common in patients from Asia (19%) and in previously treated patients (26%). CONCLUSION: Extra-pulmonary TB is common in the foreign-born population in the Calgary region, and this pattern may be more widespread than is realised. Drug-resistant strains of TB were more common in foreign-born and previously treated patients.

Asthma education and management programs in Canada.

OBJECTIVE: To establish the number and type of asthma patient education programs throughout Canada. DESIGN: National survey. SETTING: Canada. METHODS: Over a three-year period, contact was made with individuals and groups offering educational services for patients with asthma. Education given as part of a physician's consultation or a pharmacist's dispensing of medications for asthma was not considered a patient education program for the purposes of the survey. Contact was initially established by asking staff from well known asthma programs to provide lists of other such programs in their provinces or regions. Asthma programs were also identified from notices presented at Canada's Third and Fourth National Conferences on Asthma and Education. Lung associations, lay organizations and industry representatives affiliated with the Canadian Network for Asthma Care helped to supplement the list. Once identified, each patient education program was contacted by telephone and by mail to complete a 26-item questionnaire about their program. The province of Quebec was not included in the survey because it already had a province-wide, structured asthma education program and register. RESULTS: Seventy-four asthma education and management programs were identified outside Quebec. Staff in these programs were registered nurses (n=46), respiratory therapists (n=48) and other health professionals (n=21). Forty-one programs stated that at least one member of their staff had been trained as an asthma educator. In 71 programs, the initial patient encounter was of at least one hour's duration. Physician referral was required by 41 programs. The province of Quebec has a joint asthma education program provided by 114 asthma education centres throughout the province under the umbrella of the Quebec Asthma Education Network (QAEN). This comprehensive program is provided in hospitals and community centres by specialized educators - nurses, pharmacists or respiratory therapists - to patients referred by their physicians. CONCLUSIONS: A three-year search for asthma education programs in Canada identified 74 patient education programs (outside Quebec) for an asthma population estimated to exceed 1.2 million. For the province of Quebec, an integrated asthma education program is provided through a network of 114 education centres - the QAEN. The present survey shows that there has been progress in establishing asthma education programs in Canada, although there are significant regional differences in the availability of such programs.

Comparison of intramuscular betamethasone and oral prednisone in the prevention of relapse of acute asthma.

OBJECTIVE: To compare the relapse rate after a single intramuscular injection of a long acting corticosteroid, betamethasone, with oral prednisone in patients discharged from the emergency department (ED) for acute exacerbations of asthma. PATIENTS AND METHODS: Patients with acute exacerbations of asthma who were suitable for discharge from the ED were enrolled in a double-blind, randomized, placebo controlled pilot study. At discharge, patients were randomly assigned to receive either intramuscular betamethasone 12 mg and placebo capsules, or a placebo intramuscular injection and prednisone 50 mg daily for seven days. At days 7 and 21, patients were contacted by telephone to determine relapse. Relapse was defined as an unscheduled visit to a physician for treatment of continuing or worsening symptoms of asthma. RESULTS: One hundred and seventy-one patients were enrolled, of whom 87 were randomly assigned to the betamethasone group and 84 to the prednisone group. Baseline characteristics were matched evenly between the groups, with the exception of asthma duration (15.5 versus 21.2 years, respectively) and use of inhaled corticosteroids (46% versus 64.3% respectively) (P<0.05). Using intention-to-treat analysis, the relapse rates for betamethasone and prednisone at day 7 were 14.9% (13 of 87 patients) and 25% (21 of 84 patients), respectively (P=0.1), and at day 21, the rates were 36.8% (32 of 87 patients) and 31% (26 of 84 patients), respectively (P=0.4). There were no differences in symptom score, peak flows and adverse effects between the two groups at days 7 and 21. CONCLUSIONS: A single dose of intramuscular betamethasone 12 mg was safe and as efficacious as prednisone in preventing the relapse of acute asthma. There was a trend toward a reduced relapse rate at seven days. In select ED patients discharged for acute asthma, intramuscular betamethasone may be an effective alternative to prednisone.

The impact of asthma management guideline dissemination on the control of asthma in the community.

OBJECTIVE: To measure the impact of asthma management education on the control of asthma in the community. DESIGN: A cross-sectional study comparing three communities. SETTING: Three rural communities in southern Alberta. PATIENTS AND METHODS: A population sample of patients with asthma attending a pharmacy to fill a prescription for asthma medication were selected from three communities. Patients were asked to complete a questionnaire relating to their asthma management and control. INTERVENTION: Three levels of asthma management education were provided in the three communities with populations of 6000 to 10,000. The levels of education ranged from standard continuing medical education programs relating to the national asthma guidelines and a visiting asthma nurse educator to the establishment of an asthma clinic and a multiple-target, intensive education program for health professionals, town leaders, local media, schools and the public. The survey of the population with asthma was conducted approximately one year after the education program had been completed. RESULTS: A total of 327 completed questionnaires were submitted. Analysis showed that there was no significant difference that could be attributed to the intervention in the management of asthma or in the level of asthma control among the patients from the three communities. CONCLUSION: The more intense levels of education used to disseminate the content of the national asthma management guidelines did not translate into improved asthma control in the community.

Predicting emergency department utilization in adults with asthma: a cohort study.

A consecutive sample of 378 adults with asthma were assessed at a university asthma program and then interviewed 1 year later regarding their need for emergency department (E.D.) asthma treatment. The purpose of this prospective cohort study was to determine whether any of their initial features could predict their subsequent need for E.D. asthma treatment. At one year, a total of 73 of the subjects had attended emergency departments for asthma. On entry, the 73 subjects had demonstrated more self-reported lifestyle restriction from asthma and more hospital admissions E.D. visits for asthma as well as poorer asthma control or than had the 305 subjects who had not required E.D. asthma treatment since entry to the cohort. This study suggests that special attention should be paid to subjects with asthma that interferes with their lifestyle and to those who have needed hospital admission for asthma.

Extraesophageal manifestations of gastroesophageal reflux.

BACKGROUND: Associations have been reported between gastroesophageal reflux and a variety of upper and lower respiratory tract conditions. Respiratory conditions and GER are common and would be expected to coexist in many patients. Whether there is a relationship between GER and these conditions and its nature remain controversial. The purpose of this paper is to review the relationship between GER and these conditions. METHODS: Searches of the 1966 to 2000 MEDLINE database were undertaken to identify appropriate studies. The terms gastroesophageal reflux, medical antireflux therapy, and antireflux surgery were combined with rhinitis, sinusitis, laryngitis, laryngeal stricture, croup, apnea, dental caries, aspiration pneumonia, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, COPD, chronic bronchitis, bronchiectasis and cough. RESULTS: Papers were identified that related any of the above respiratory conditions to gastroesophageal reflux or to antireflux therapy. Most suggested a causative relationship between GER and these conditions but only a few of the studies were controlled. Controlled studies demonstrate a strong association between GER and asthma and cystic fibrosis. CONCLUSIONS: A strong association between GER and some respiratory conditions has been demonstrated in controlled trials. It is uncertain whether the association is due to GER causing respiratory disease or vice versa. It is clear that further properly powered, controlled, randomized trials of the relationship between GER and antireflux therapy and respiratory disease need to be conducted.

Comparison of once- with twice-daily dosing of fluticasone propionate in mild and moderate asthma.

OBJECTIVES: Two 12-week, randomized, double-blind, parallel-group studies were performed to compare the efficacy and safety of once- and twice-daily dosing of fluticasone propionate (FP) in the treatment of mild to moderate asthma, considered to require the equivalent of either 200 or 500 microg of FP daily. PATIENTS AND METHODS: In study A, 461 patients with asthma received FP either 200 microg once daily or 100 microg twice daily. In study B, 443 patients with asthma received FP, either 500 microg once daily or 250 microg twice daily. RESULTS: In both studies, regardless of the treatment regimen to which patients were randomly assigned, small improvements over baseline were observed in morning peak expiratory flows (PEF) and forced expiratory volume in 1 s (FEV1) following 12 weeks of treatment. In study A, the mean morning PEF improved by 2.4% and 4.3% (once daily versus twice daily, P=0.008). In study B, the mean morning PEF improvement was 0.2% and 3.7% (once daily versus twice daily, P<0.001). For both studies, the increases observed in FEV1 were not significantly different between the two groups (P = not significant). The incidence of exacerbations of asthma and related events was 13% and 5%, respectively, in the patients with mild asthma for the once-daily group versus the twice-daily group; these exacerbations were 12% and 10%, respectively, in patients with moderate asthma. Otherwise, the incidence and types of adverse events were comparable for the two treatment regimens. Although twice-daily dosing demonstrated small but statistically significant improvements over once-daily dosing, patients of both groups generally maintained a good level of asthma control on both regimens according to current treatment guidelines. CONCLUSIONS: Twice-daily dosing of FP is more effective than once-daily dosing, although the latter can maintain asthma control in most patients.

Lung health among electricians in Edmonton, Alberta, Canada.

Respiratory symptoms, lung function, and radiographic changes among 100 actively employed electricians in Edmonton, Alberta, Canada, with 20 or more years of union membership were compared with those of 100 telephone workers. Posteroanterior chest radiographs were evaluated by two experienced chest physicians, with a third arbitrating films that were disagreed upon. Employment in a number of industrial sectors was compared for time and for time-weighted exposure to dust and fumes. Compared with telephone workers, electricians had more usual cough (odds ratio [OR] = 3.36; 95% confidence interval [CI], 1.36-8.31), usual phlegm (OR = 2.44; 95% CI, 1.01-5.86), chronic phlegm (OR = 2.74; 95% CI, 1.13-6.60), and shortness of breath (OR = 2.26; 95% CI, 1.10-4.67), but no differences in lung function. The prevalence of radiographic changes in both groups was low. The electricians had more radiographic changes, but only for the category "any change" was the difference statistically significant (OR = 5.2; 95% CI, 1.06-23.93). Only two electricians had small irregular opacities. Phlegm, chronic phlegm, and chest tightness were significantly associated with cumulative exposure to fumes in the gas and oil industry and to total industrial construction.

Lung health among boilermakers in Edmonton, Alberta.

BACKGROUND: Construction boilermakers may be exposed to a variety of substances, including asbestos and welding fumes. Past studies of boilermakers have shown increases in mortality from lung cancer and asbestosis and radiographic changes consistent with asbestos exposure. METHODS: Respiratory symptoms, lung function, and radiographic changes were compared for 102 actively employed boilermakers with 20 or more years of union membership and 100 telephone workers. Posteroanterior chest radiographs were evaluated by two experienced chest physicians, with a third arbitrating disagreed films. Union members were further categorized as boilermakers (n = 50) or welders (n = 52), based on longest service. Lung health was also compared with employment in a number of work sectors for time, and time-weighted exposure to dust and fumes. RESULTS: Boilermakers had more respiratory symptoms than telephone workers, but lung function did not differ. Radiographic changes were more common among the boilermakers (20% with any change, 8% circumscribed, and 9% diffuse pleural thickening). None of the boilermakers had small radiographic opacities. Several symptoms suggestive of bronchial responsiveness were associated with fume exposures in the gas and oil industry. Workers whose longest service was as a boilermaker demonstrated more symptoms than did welders. FEV1, FEV1/FVC, FEF25-75, and FEF50 were significantly lower among boilermakers compared with welders. CONCLUSION: Health screening programs for these workers are warranted.

Tuberculosis among immigrants: interval from arrival in Canada to diagnosis. A 5-year study in southern Alberta.

OBJECTIVE: To examine the pattern of tuberculosis (TB) occurring among immigrants and the interval from arrival in Canada to diagnosis of the disease. DESIGN: Study of all cases of TB diagnosed in foreign-born residents of southern Alberta during the 5-year period 1990-1994. SETTING: A centre for the diagnosis, management and control of all cases of TB in the southern half of the province of Alberta. METHODS: All foreign-born patients in whom TB was newly diagnosed between January 1990 and December 1994 were included in the study. The interval from their arrival in Canada to diagnosis, their country of birth and the site of their disease were documented. RESULTS: Immigrants to Canada accounted for 248 (70.6%) of the 351 cases of TB diagnosed in southern Alberta during the 5-year period. The majority of these immigrants (182/248 [73.4%]) were of Asian origin. Extrapulmonary TB accounted for 111 (61.0%) of the 182 cases of the disease in Asian immigrants. The mean period between immigration and diagnosis was 11.2 years (standard deviation [SD] 13.9 years). Half of the patients presented within 7 years of their arrival in Canada. The time to presentation was shortest for patients with superficial lymph node disease (mean 7.6 years [SD 6.9] after arrival), intermediate among those with extrapulmonary disease, excluding superficial disease of the lymph node (10.1 years [SD 12.1]), and longest for those with pulmonary disease (14.2 years [SD 17.2]). TB developed sooner after arrival in Canada among immigrants from Asian countries (mean 9.1 years) than among those from other countries (17.2 years) (p = 0.01). CONCLUSIONS: Given the low annual incidence of TB in Canada (7.1 per 100,000), it is probable that TB occurring among immigrants reflects infection acquired before arrival in Canada. Health care professionals need to be aware that immigrants from countries with a relatively high prevalence of TB remain at risk for the disease (often at an extrapulmonary site) for many years after they immigrate to low-prevalence countries.

The influence of silicosis on deteriorating lung function in gold miners.

STUDY OBJECTIVE: To reexamine the symptoms, lung function, and chest radiographs of older gold miners who continued to work in or around gold mines 5 years after their enrollment in the cohort. DESIGN: A follow-up study of a stratified sample of a cohort of gold miners. SETTING: A health-care center for 24 gold mines in Welkom, South Africa. POPULATION: A stratified, random sample of 242 miners who were part of a cohort of 1,197 gold miners who had been employed underground in gold mines for a mean period of 29 years. No silicosis was apparent on entry in 59 men, 78 had silicosis with category 1 nodule profusion, 73 had category 2, and 32 had category 3. MEASUREMENTS: The men were assessed with questionnaires, lung function tests, and chest radiographs approximately 4.5 years after their initial assessment. RESULTS: Radiologic features of silicosis had progressed an average of one subcategory (eg, 2/1 to 2/2) in the follow-up period. Lung function deteriorated more rapidly in the men with silicosis and the deterioration increased in proportion to the degree of silicosis at the start of the study. Thus, the annual loss of FEV1 was 37 mL in those without silicosis, 57 mL in those with category 1, 100 mL with category 2, and 128 mL in the men with category 3 nodule profusion (p=0.000001). A similar pattern of loss was noted for the FVC (p=0.00003) and the single-breath lung diffusion (p=0.004). These changes remained significant after controlling for age, original lung function, and for smoking. CONCLUSIONS: The men with silicosis suffered a substantial loss of lung function during the period of follow-up that was directly in proportion with the nodule profusion on their initial chest radiographs.

Lung health among plumbers and pipefitters in Edmonton, Alberta.

OBJECTIVES: A cross sectional study was undertaken to assess lung health among plumbers and pipefitters. Respiratory symptoms, lung function, and radiographic changes among 99 actively employed plumbers and pipefitters with > or = 20 years of union membership were compared with 100 telephone workers. METHODS: A respiratory symptom questionnaire was administered, including smoking and occupational histories. Spirometry was conducted according to standard criteria. Posteroanterior chest radiographs were evaluated by two experienced chest physicians, with a third arbitrating disagreed films. Members of the union were categorised as pipefitters (n = 57), plumbers (n = 16), or welders (n = 26), based on longest service, and compared with the telephone workers and internally (between groups). Lung health was also compared with employment in several work sectors common to Alberta for time, and for time weighted by exposure to dust and fumes. RESULTS: Compared with the telephone workers, plumbers and pipefitters had more cough and phlegm, lower forced vital capacity, and more radiographic changes (20% with any change), including circumscribed (10%) and diffuse pleural thickening (9%). None of the plumbers and pipefitters had small radiographic opacities. Among the three subgroups of workers, plumbers had the highest prevalence of radiographic changes. Both plumbers and pipefitters showed higher odds ratios for cough and phlegm than the welders. No differences between groups were found for lung function. Indicators of lung health were not related to work in any sector. CONCLUSIONS: Plumbers and pipefitters had increased prevalence of symptoms suggestive of an irritant effect with no evidence of bronchial responsiveness. The chest radiographs showed evidence of asbestos exposure, especially in the plumbers, but at lower levels than previously reported. Health screening programmes for these workers should be considered, although the logistical problems associated with screening in this group would be considerable.

The effect of a peak flow-based action plan in the prevention of exacerbations of asthma.

STUDY OBJECTIVE: To determine the effect of a symptom-based and a peak flow-based action plan in preventing acute exacerbations in subjects with poorly controlled asthma. DESIGN: A randomized controlled trial in which subjects who had required urgent treatment for their asthma were allocated to receive no action plan, a symptom-based plan, or a peak flow-based action plan. SETTING: A university hospital asthma clinic. POPULATION: One hundred fifty subjects were recruited after attending an emergency department or a clinic for urgent treatment of asthma. INTERVENTIONS: All subjects received evaluation and education for asthma before being randomly allocated to receive no action plan, a symptom-based action plan, or a peak flowmeter and a peak flow-based action plan. MEASUREMENTS: Subjects were assessed by questionnaire at 3 and 6 months after enrollment with questions relating to their asthma control and their need for urgent treatment or hospital admission for asthma. RESULTS: At 6 months after enrollment, although all three intervention groups experienced improvement in their asthma control, there was a striking reduction in emergency department visits for asthma only in the peak flow-based action plan group (p=0.006). No significant difference in emergency visits was apparent between the symptom-based action plan and no action plan groups. CONCLUSIONS: We conclude that a peak flow-based action plan is effective, at least in the short term, in protecting patients with asthma against severe exacerbations of their disease.

Antituberculosis drug resistance in immigrants to Alberta, Canada, with tuberculosis, 1982-1994.

SETTING: Provincial Tuberculosis Service, Alberta, Canada. OBJECTIVE: To estimate resistance rates of Mycobacterium tuberculosis to antituberculosis drugs in relation to previous treatment, country of origin, age and duration of residence in Canada. DESIGN: Retrospective chart review of all culture-positive tuberculosis diagnosed between 1982 and 1994 in immigrants to Alberta. RESULTS: A total of 753 immigrants with culture-positive tuberculosis were studied; 131 patients (17.4%, 95% Confidence Interval [CI] 14.7, 20.1) had strains resistant to one or more of the first-line medications (isoniazid [INH], rifampin [RIF], ethambutol [EMB], pyrazinamide [PZA], and streptomycin [SM]). Initial and secondary resistance rates were 16.4% and 30.3%, respectively (P = 0.003, Odds ratio [OR] 2.2, 95% CI 1.3, 3.8). Resistance occurred in 22.2% of patients 40 years of age and under, and in 13.8% of those over 40 years of age (P = 0.005, OR 1.8, 95% CI 1.2, 2.6). Resistant M. tuberculosis was isolated from 20.4% of those who had lived in Canada for less than 15 years, and in 9.0% of those who had immigrated to Canada more than 15 years before diagnosis (P < 0.001; OR 2.4, 95% CI 1.3, 4.2). Resistance rates to individual medications in all immigrants were as follows: INH 9.9% (95% CI 7.8, 12.0), RIF 0.8% (95% CI 0.2, 1.4), EMB 1.9% (95% CI 1.0, 2.8), PZA 1.9% (95% CI 0.3, 3.5), and SM 12.9% (95% CI 10.4, 15.4). Immigrants from Vietnam, China, and the Philippines had tuberculosis strains that were resistant to one or more of the first line medications in 30.2%, 21.8%, and 15.5% of cases, respectively (P = 0.04). CONCLUSION: In industrialized countries such as Canada where most cases of tuberculosis are diagnosed among the foreign-born, drug resistance surveys continue to be an important part of an effective tuberculosis control program.

Extra-pulmonary tuberculosis: a high frequency in the absence of HIV infection.

SETTING: A tuberculosis centre for the diagnosis, management and control of all tuberculosis in a region in Western Canada with a population of approximately 1.2 million. OBJECTIVE: To measure the proportion of cases of extra-pulmonary tuberculosis in relation to country of birth, age and gender of the subject. DESIGN: A prospective study of all patients with tuberculosis diagnosed during a five-year period, 1990-1994. Information relating to age, country of birth and details relating to their tuberculosis were all gathered and stored on a computerised tuberculosis register. RESULTS: A total of 351 patients with tuberculosis were diagnosed during the five-year period. Extra-pulmonary tuberculosis, defined as disease which, with the exception of miliary tuberculosis, was not associated with lung involvement, was diagnosed in 160 (46%) of the patients. The incidence of extra-pulmonary tuberculosis, especially lymph node disease, tended to be higher in younger patients but was significantly higher in immigrants from Asia in whom the majority (61%) presented with extra-pulmonary disease. Less than 2% of the subjects in this study were infected with the human immunodeficiency virus (HIV). CONCLUSION: Extra-pulmonary tuberculosis accounted for approximately half of the cases of tuberculosis in a western Canadian tuberculosis centre. This high frequency of extra-pulmonary disease was not attributable to HIV infection.

Asthma in goldminers.

OBJECTIVES: To determine whether asthma in goldminers is caused by or contributed to by their working environment. DESIGN: A case-control study in which men with asthma working underground in goldmines were compared with underground goldminers without asthma in relation to their age, duration of exposure to the underground environment, atopy and family history of asthma. SETTING: An in- and outpatient facility providing for the medical needs of approximately 90 000 miners employed on goldmines in the Free State. OUTCOME MEASURES: Occupational history, atopy and family history of asthma were compared in the two groups. The age of onset of asthma and duration of occupational exposure were examined in the men with asthma. RESULTS: The study sample included 78 underground miners with asthma and 46 without asthma. The men in the two groups were of similar age, but those with asthma had worked underground for a longer period than the men without asthma. Twenty of the asthmatic and none of the control group had been exposed to paint and cement in the course of their work. Fifty of the asthmatic and only 3 of the control group were atopic. The mean age of onset of asthma (+/-SD) was 30.6 +/- 10.73 years. Six of the men had developed asthma before starting to work in the mines, and the disease had developed 13.4 +/- 8.22 years after starting to work underground in the remaining 72. CONCLUSION: The late age of onset and the onset after exposure to the underground environment suggest that the disease was work-related.

Short course chemoprophylaxis with rifampicin, isoniazid and pyrazinamide for tuberculosis evaluated in gold miners with chronic silicosis: a double-blind placebo controlled trial.

SETTING: A medical facility for approximately 90,000 gold miners employed on 24 South African gold mines. OBJECTIVE: To evaluate the effectiveness of rifampicin, isoniazid and pyrazinamide given for 3 months for the prevention of tuberculosis in men with silicosis. DESIGN: A randomised double-blind placebo controlled trial with active 4-year follow up of subjects by routine radiographic screening. RESULTS: A total of 382 gold miners with silicosis were randomised to receive rifampicin 600 mg, isoniazid 400 mg and pyrazinamide 1.25 g daily as Rifater or a placebo. These men have been followed for 4 years since the end of the treatment period. Eleven men who received the combination tablet and 15 men who received the placebo tablet have developed tuberculosis (chi 2 df1 = 0.66, P = 0.4). CONCLUSION: This multi-drug short course chemoprophylaxis regimen has failed to prevent tuberculosis in miners with silicosis. Even if a larger study had demonstrated a statistically significant effect of the regimen as compared with placebo, the rate of tuberculosis in the men who received the three-drug regimen was unacceptably high.