Long-term economic evaluation of intensive patient education during the first treatment year in newly diagnosed adult asthma.

The cost-effectiveness of intensive patient education of guided asthma self-management given during the first treatment year was evaluated after 5 years of follow-up. Consecutive, newly-diagnosed asthmatics (n = 162, age 18-76 years) were randomized for intensive (80 patients) vs. conventional patient education. Effectiveness was evaluated in terms of lung functions, airway hyperresponsiveness (PD15), and quality of life as measured by the generic 15D and disease-specific St. George's Respiratory Questionnaire (SGRQ). Total treatment costs were also estimated. All patients had anti-inflammatory treatment from the beginning. Sixty-four intervention group (IG) patients and 70 control group (CG) patients were evaluated after 5 years. Forced expiratory volume in 1 sec (FEV1) improved only in the IG, and only during the first treatment year. However, PD15 improved throughout the follow-up. The unscheduled healthcare costs were significantly higher in the CG than in the IG (P = 0.04) and the relative risk for sickness days due to asthma was lower in the IG than in the CG, odds ratio 0.33 (95% CI 0.28; 0.40). However, because there was no significant difference between the groups in any outcome variable or in total costs at 5 years, the incremental cost-effectiveness ratio could not be calculated. The first year intervention had only a short-term beneficial treatment effect, which the CG could catch up during the two last follow-up years, except in FEV1. The peak expiratory flow (PEF)-based self-management had no advantage over the symptom-based self-management. However, the intervention had a consistent tendency of being less costly in the long-run. It is possible to conclude tentatively that regular effective medical treatment and control visits during the first treatment year is at least as important for the long-term treatment result as intensive patient education.

Long-term (3-year) economic evaluation of intensive patient education for self-management during the first year in new asthmatics.

Patient education and self-management programmes have proved effective in many studies with short follow-up periods. We studied the 3-year cost-effectiveness of an intensive programme of patient education and supervision for self-management. The study consisted of 162 consecutive newly diagnosed asthmatics who were randomized either into an intervention group (IG) receiving intensive patient education and supervision for self-management at an outpatient clinic during the first year, or a control group (CG) receiving conventional education at the baseline visits only. Both groups had 2 additional years of follow-up. Lung functions and health-related quality of life (HRQOL) were measured. Extra direct and indirect costs were recorded. At 3 years the differences in forced expiratory volume in 1 s (FEV1) and in peak expiratory flow (PEF) were significantly better in the IG being in (% predicted) respectively 5.3 (95% CI 0.6-10.0) and 4.4 (95% CI 0.1-8.7), (P < 0.05). The airway responsiveness (PD15) did not differ significantly, but the improvement from baseline to 3 years was significantly greater in the IG, being 0.40 dose steps (95% CI 0.05-0.75) (P < 0.05). HRQOL scores did not differ significantly. The risk for sickness day was less in the IG with a RR of 0.6 (95% CI 0.50-0.69) (P = 0.000) and among patients who used the PEF meter. The compliance was similar in both groups when measured by the PEF-based self-management. There was no statistically significant difference in costs, although there was a consistent tendency for lower costs in the intensive programme. The intensive programme was more effective in terms of FEV1, PEF and improvement in PD15 and equally effective in terms of other lung functions and HRQOL, but there was no clear difference in the costs.

The South Karelia Air Pollution Study: changes in respiratory health in relation to emission reduction of malodorous sulfur compounds from pulp mills.

The authors assessed the health effects of emission reduction of malodorous sulfur compounds in a prospective cohort study with a controlled natural experiment. A total of 810 subjects (83%) participated in the follow up: 316 from the severely polluted, 306 from the moderately polluted, and 188 from the nonpolluted communities. In the severely polluted community, the annual ambient air concentration of total reduced sulfur compounds decreased from 11 microg/m3 to 6 microg/m3. Compared with the nonpolluted community, the relative decrease in acute respiratory infections, adjusted for a change in smoking habits, was 0.53 episodes/person-year (95% confidence interval = 0.22, 0.83) in the severely polluted community and 0.36 episodes/person-year (95% confidence interval = 0.06, 0.66) in the moderately polluted community. In addition, the frequency of nasal symptoms (p = .004) and cough (p = .037) decreased significantly. The results are consistent with the hypothesis that exposure to malodorous sulfur compounds increases the risk of acute respiratory infections and symptoms of the respiratory tract.

Quality-of-life measures and clinical parameters in asthmatics during three year follow-up.

Two types of health-related quality-of-life (HRQoL) index, the disease-specific St George's Respiratory Questionnaire (SGRQ) and the generic 15D, were compared for indication of HRQoL changes and correlation with clinical parameters in 157 newly diagnosed asthmatics. The asthmatics were treated with inhaled anti-inflammatory therapy. Measurements at baseline, and after one and three years treatment. Both HRQoL indices indicated a significant improvement in HRQoL during treatment. The changes in total HRQoL scores correlated moderately well. Changes in airway responsiveness correlated fairly well with those of the total SGRQ score (r = 0.29 between baseline and one yr treatment and 0.36 between baseline and three yrs treatment, p < 0.001) and with those of 15D (r = 0.21 between baseline and three yrs treatment; p < 0.05). This may indicate that airway hyperresponsiveness influences the personal assessment of HRQoL. On the other hand, the varying correlation between lung function and HRQoL scores may indicate that they measure largely unrelated factors. Both the disease-specific and the generic health-related quality-of-life indices changed with treatment and indicated an improved health-related quality-of-life for mild asthmatics during a three-year treatment.

Comparison of a Multidose Powder Inhaler Containing Beclomethasone Dipropionate (BDP) with a BDP Metered Dose Inhaler with Spacer in the Treatment of Asthmatic Patients.

OBJECTIVE: The clinical efficacy, tolerability and acceptability of a new multidose powder inhaler (MDPI) [Easyhaler((R)), Orion Pharma, Finland] containing a high dose (500 microg/dose) of beclomethasone dipropionate (BDP) were compared with those of BDP metered dose inhaler administered with a large volume spacer (MDI-spacer). PATIENTS AND STUDY DESIGN: Recruited patients were adult asthmatics currently receiving 800 to 1000 microg/day of inhaled corticosteroid. The dose of BDP during the study was 1000 mg/day. The study was an open, randomised, parallel-group multicentre study and included a 2-week run-in period followed by a 12-week treatment period. RESULTS: 74 patients were randomised to both groups. During the run-in period the mean morning peak expiratory flow (PEF) was 489 and 478 L/min in the MDPI and MDI-spacer groups, respectively. During the last 2 weeks of the study the morning PEF was 485 L/min in the MDPI group and 477 L/min in the MDI-spacer group. Asthma symptom scores and use of rescue medication were low in both groups. The median dose of histamine required to decrease forced expiratory volume in 1 second (FEV(1)) by 15% was 1.05mg in the MDPI group and 0.64mg in the MDI-spacer group. The most frequent adverse events were hoarseness and sore throat. Mean serum cortisol levels were not affected in either treatment group. Patients' personal opinion regarding acceptability of the devices clearly favoured the MDPI. CONCLUSION: In conclusion, the novel powder inhaler was well tolerated and at least equally effective compared with the conventional MDI-spacer combination in the treatment of asthma with BDP. However, in everyday use the patients clearly favoured the powder inhaler.

The South Karelia Air Pollution Study: effects of low-level exposure to malodorous sulfur compounds on symptoms.

Exposure to very low levels of ambient-air malodorous sulfur compounds and their effect on eye irritation, respiratory-tract symptoms, and central nervous system symptoms in adults were assessed. A cross-sectional self-administered questionnaire (response rate = 77%) was distributed during March and April 1992 to adults (n = 336) who lived in a neighborhood that contained a pulp mill and in a nonpolluted reference community (n = 380). In the exposed community, the measured annual mean concentrations of total reduced sulfur compounds and sulfur dioxide measured in two stations were 2 to 3 micrograms/m3 and 1 micrograms/m3, respectively. In the reference community, the annual mean concentration of sulfur dioxide was 1 micrograms/m3. The residents of the community near the pulp mill reported an excess of cough, respiratory infections, and headache during the previous 4 wk, as well as during the preceding 12 mo. The relative risk for headache was increased significantly in the exposed community, compared with the reference area: the adjusted odds ratio (aOR) was 1.83 (95% confidence interval [95% CI] = 1.06-3.15] during the previous 4 wk and 1.70 (95% CI = 1.05-2.73) during the preceding 12 mo. The relative risk for cough was also increased during the preceding 12 mo (aOR = 1.64, 95% CI = 1.01-2.64). These results indicated that adverse health effects of malodorous sulfur compounds occur at lower concentrations than reported previously.

South Karelia Air Pollution Study: daily symptom intensity in relation to exposure levels of malodorous sulfur compounds from pulp mills.

In a longitudinal study, we assessed the relation between daily exposure to ambient air malodorous sulfur compounds from pulp production and experience of symptoms in a small population living in the vicinity of a pulp mill. Special emphasis was laid on exposure-response pattern, where the intensity of the symptoms of interest was assessed in six consecutive questionnaires after three predefined levels of exposure to malodorous sulfur compounds [total reduced sulfur (TRS)] (reference: daily mean < 10 micrograms/m3, medium exposure: 10-30 micrograms/m3 high exposure: > 30 micrograms/m3). The study population included 81 adults, who responded to the baseline questionnaire (response rate 81%). The outcomes of interest were eye, respiratory, and central nervous symptoms. The mean daily intensity of the outcome symptoms, but not of control symptoms, was significantly higher on days of medium and high exposure compared with the reference days (paired t test). The probability ratios between experiencing more or fever symptoms during the medium and high exposure compared with reference days were increased for all the symptoms of interest with a consistent exposure response pattern. The probability ratios were for eye symptoms 3.17, 95% confidence intervals (CI) 1.21 to 7.47 (medium exposure), and 5.0, 95% CI 1.66 to 12.65 (high exposure); for nasal symptoms 3.13, 1.25 to 7.25 (medium), and 8.50, 3.19 to 18.64 (high); and for pharyngeal symptoms 2.0, 0.92 to 4.14 (medium) and 5.20, 1.95 to 11.99 (high). The results suggest that relatively low daily levels of malodorous sulfur compounds (TRS > 10 micrograms/m3) cause exposure-related short-term adverse effects.

The South Karelia Air Pollution Study: the effects of malodorous sulfur compounds from pulp mills on respiratory and other symptoms in children.

We assessed the role of long-term exposure to ambient air malodorous sulfur compounds released from pulp mills as a determinant of eye and respiratory symptoms and headache in children. Adverse health effects of environmental exposure to these compounds in children have not been reported previously. The parents of 134 children living in a severely polluted (n = 42), moderately polluted (n = 62) and rural nonpolluted (n = 30) community responded to a cross-sectional questionnaire. The response rate was 83%. The adjusted odds ratios (OR) for symptoms experienced during the previous 4 weeks and 12 months in the severely versus nonpolluted community were estimated in logistic regression analysis controlling for age and gender. The risk of nasal symptoms (4 weeks OR 1.40, 95% CI 0.59-3.31; 12 months OR 2.47, 95% CI 0.93-6.53), cough (4 weeks OR 1.83, 95% CI 0.75-4.45; 12 months OR 2.28, 95% CI 0.95-5.47), eye symptoms (12 months OR 1.15, 95% CI 0.43-3.05), and headache (12 months OR 1.77, 95% CI 0.69-4.54) was considerably increased in the severely polluted community, although not quite reaching statistical significance. The results suggest that exposure to malodorous sulfur compounds may affect the health of children.

Leukotriene E4 and granulocytic infiltration into asthmatic airways.

Sulphidopeptide leukotrienes are potent bronchoconstrictors and increase bronchial hyperreactivity, one of the hallmarks of asthma. We have demonstrated that leukotriene LTE4, the most stable of the sulphidopeptide leukotrienes, elicited an increase in the numbers of eosinophils and neutrophils in the lamina propria of the airway mucosa 4 h after inhalation in 4 asthmatic subjects. The numbers of eosinophils were, on average, 10-fold greater than those of neutrophils. There was no significant change in numbers of lymphocytes, plasma cells, mast cells, or macrophages. Since LTE4 recruits granulocytes, the potential of antisulphidopeptide leukotriene drugs as anti-inflammatory and "steroid-sparing" agents should be tested.

The South Karelia Air Pollution Study: acute health effects of malodorous sulfur air pollutants released by a pulp mill.

We evaluated the acute health effects of a strong emission of malodorous sulfur compounds released from a pulp mill in South Karelia, Finland. The 24-hour ambient air concentrations of hydrogen sulfide for the two emission days were 35 and 43 micrograms/m3 (maximum 4-hour 135 micrograms/m3). A questionnaire was distributed after the high exposure and later after a low exposure period to 29 households with 75 subjects living in the nearby community. During the high exposure, 63% of the respondents reported experience of at least one symptom compared to 26% during the reference period. Every third participant reported difficulties in breathing. In the 45 subjects responding to both questionnaires more eye, respiratory and neuropsychological symptoms occurred during the exposure compared to the reference period. The strong malodorous emission from a pulp mill caused an alarming amount of adverse effects in the exposed population.

Exposure to hydrogen sulphide and respiratory function.

A study was carried out to assess possible effects of low concentrations of hydrogen sulphide on respiratory function. The cohort comprised 26 male pulp mill workers (mean age 40.3, range 22-60 years) with a daily exposure to hydrogen sulphide in the workplace, and 10 volunteers, who had asthma (three men, mean age 40.7, range 33 to 50 years, and seven women, mean age 44.1, range 31 to 61 years). The respiratory function of the pulp mill workers was monitored by measuring forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and bronchial responsiveness after at least one day off work and at the end of a workday. Bronchial responsiveness was tested by challenge with histamine. The 10 asthmatic subjects were exposed in laboratory conditions to 2 ppm of hydrogen sulphide for 30 minutes in an exposure chamber. Airway resistance (Raw) and specific airway conductance (SGaw) were assessed by a body plethysmograph, and the ventilatory capacities were measured with a flow volume spirometer. No significant changes in respiratory function or bronchial responsiveness related to exposure to hydrogen sulphide in the pulp mill workers were found. In the asthmatic subjects, Raw was increased by 26.3% and SGaw was decreased by 8.4% on average after exposure to hydrogen sulphide. These changes were not statistically significant. In two subjects, however, changes were greater than 30% in both Raw and SGaw, indicating bronchial obstruction. It is concluded that exposure for a relatively short time to hydrogen sulphide concentrations appreciably higher than those existing in ambient air do not cause noticeable effects on respiratory function.

The South Karelia Air Pollution Study. The effects of malodorous sulfur compounds from pulp mills on respiratory and other symptoms.

The paper mills in South Karelia, the southeast part of Finland, are responsible for releasing a substantial amount of malodorous sulfur compounds such as hydrogen sulfide (H2S), methyl mercaptan (CH3SH), and methyl sulfides [(CH3)2S and (CH3)2S2], into ambient air. In the most polluted residential area the annual mean concentrations of hydrogen sulfide and methyl mercaptan are estimated to be 8 and 2 to 5 micrograms/m3 and the highest daily average concentration 100 and 50 micrograms/m3. The annual mean and highest daily concentrations of sulfur dioxide (SO2) are very low. We studied the effects of malodorous sulfur compounds on eye, nasal and respiratory symptoms, and headache in adults. A cross-sectional self-administered questionnaire was distributed in February 1987 and responded to by 488 adults living in a severely (n = 198), a moderately (n = 204), and a nonpolluted community (n = 86). This included questions about occurrence of the symptoms of interest during the previous 4 wk and 12 months and individual, behavioral, and other environmental determinants of the symptoms. The response rate was 83%. The odds ratios (OR) for symptoms experienced often or constantly in severely versus nonpolluted and moderately versus nonpolluted communities were estimated in logistic regression analysis controlling potential confounders. The odds ratios for eye (moderate exposure OR 11.70, Cl95% 2.33 to 58.65; severe exposure OR 11.78, Cl95% 2.35 to 59.09) and nasal symptoms (OR 2.01, Cl95% 0.97 to 4.15; OR 2.19, Cl95% 1.06 to 4.55) and cough (OR 1.89, Cl95% 0.61 to 5.86; OR 3.06, Cl95% 1.02 to 9.29) during the previous 12 months were increased, with a dose-response pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral ofloxacin once daily and doxycycline in the treatment of acute exacerbations of chronic bronchitis.

192 patients, most of them ambulatory, with acute exacerbation of chronic bronchitis were treated with 10- to 14-day courses of oral ofloxacin receiving 400 mg once daily or doxycycline first 200 mg and then 100 mg once daily in this randomized observer-blinded multicentre study. 98 patients were included in the ofloxacin group and 94 in the doxycycline group. The clinical efficacy was 86/87 (98.8%) in the ofloxacin group and 87/91 (91.2%) in the doxycycline group. The bacteriological efficacy was 31/34 (91.2%) in the ofloxacin group and 19/24 (79.2%) in the doxycycline group. Some patients had more than one pathogen. There was no statistically significant difference in efficacy between the two treatment groups; both treatments were highly effective and well tolerated. The adverse events showed an expected pattern. Ofloxacin treatment was discontinued in three patients. In conclusion, both treatments were found to have similar safety and efficacy and were well tolerated when used for treatment of acute exacerbations of chronic bronchitis.

Once-daily theophylline in the treatment of nocturnal asthma.

The efficacy and side-effects of individually adjusted doses of controlled-release theophylline given once daily in the evening (average dose 650 mg) were compared with those of standard treatment with controlled-release terbutaline 7.5 mg b.d. Thirty-six asthmatics with regular morning obstruction ("morning dipping") were studied over two treatment periods each of two weeks, according to a crossover, randomized, double blind design. Morning peak expiratory flow (PEF) was slightly but significantly higher with theophylline (363 l.min-1) than terbutaline (342 l.min-1). Feelings of dyspnoea on waking in the morning were also less pronounced with theophylline. There were no other differences between the treatment periods during the day or night, with respect to dyspnoea or any the other symptoms. Side-effects were mild and were reported with similar frequencies during both treatments. It is concluded than an individually adjusted dose of once-daily theophylline administered in the evening is at least as effective as conventional therapy with controlled-release terbutaline in preventing nocturnal and early morning asthma, when both drugs are added to regular medication with inhaled sympathomimetics and steroids.

Psychosocial effects of continuous oxygen therapy in hypoxaemic chronic obstructive pulmonary disease patients.

Twenty six hypoxaemic patients with severe and stable chronic obstructive pulmonary disease (COPD) were treated with continuous domiciliary oxygen for a six month period. The patients were evaluated 1, 3 and 6 months after the start of oxygen therapy. In addition to blood gas analysis, 15 coping skills were evaluated by the patient and by the nurse, who also rated the general activity of the patients. Depression was measured by Beck Depression Inventory (BDI) at the start of the trial and after six months' oxygen therapy. The general psychosocial response was meagre; no significant changes were observed in any psychosocial measures. The response was slightly better in younger and less hypoxaemic patients. We conclude that the psychosocial response to oxygen therapy in severely hypoxaemic COPD patients is limited.

The superiority of combination beclomethasone and salbutamol over standard dosing of salbutamol in the treatment of chronic asthma.

We studied the clinical effect of a combination aerosol containing salbutamol and beclomethasone dipropionate in comparison to doubling the standard dose of salbutamol from an inhaler. Fifty-seven patients completed the double-blind, crossover study. They were treated with either an aerosol of 100 micrograms beclomethasone dipropionate and 200 micrograms salbutamol or 400 micrograms salbutamol alone. Both regimens were administered four times a day for 4 weeks. The patients showed significant improvement in FEV1, PEFR, and symptom scores after treatment with beclomethasone dipropionate and salbutamol compared with pre-trial values and with treatment with double the dose of salbutamol. The patients demonstrated a clear preference for treatment with the combination of beclomethasone dipropionate and salbutamol. Regular treatment with beclomethasone dipropionate in addition to salbutamol as a combination inhaler provides much better control of asthma than merely increasing the dose of salbutamol in those patients poorly controlled on standard doses of inhaled bronchodilators.