Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study.

UNLABELLED: We evaluated asthma control and medication use 5 years after introduction of an inhaled corticosteroid (budesonide via Turbuhaler) in 462 patients with persistent asthma and symptoms of different duration. An early treatment group with symptoms for <2 years (group A) was compared with a delayed treatment group (group B) (median duration 5 years and 3 months). Most patients received budesonide 400 microg twice daily as initial dose. We report 5-year follow-up data on 404 patients (group A n = 253; group B n = 151) and on a few more patients after treatment for 6 months, 1 year and 3 years. At 5 years the mean maintenance doses of budesonide were 412 microg (A) and 825 microg (B), respectively (P<0.001). Nevertheless, treatment goals (normal lung function, normal exercise tolerance, minimal use of reliever medication, no asthma exacerbations) were all statistically significantly more frequently achieved in group A. At 5 years group B patients also used significantly more additional asthma medications, e.g. inhaled long-acting beta2-agonists by 64% compared with 6% in group A. In group A 43 patients (17%) had been able to stop budesonide treatment compared to five patients (3%) in group B. A subgroup of group B patients with higher mean baseline FEV1 values than group A showed nevertheless significantly poorer response. No treatment-related serious adverse events were reported. Budesonide was well tolerated in both groups. CONCLUSION: Duration of asthma symptoms when starting treatment with an inhaled corticosteroid is an important determinant for the response. Early treatment gives significantly better airway function and asthma control than delayed treatment and at lower maintenance doses.

Lung deposition and protective effect of terbutaline delivered from pressurized metered-dose inhalers and the Turbuhaler in asthmatic individuals.

We investigated the relationship between pulmonary deposition of terbutaline and bronchoprotection against methacholine and histamine with the Turbuhaler (AstraZeneca, Lund, Sweden) and a pressurized metered dose inhaler (pMDI) in 13 asthmatic patients. The study was done with a randomized, double blind, double dummy, and crossover design. On different days, the provocative concentration of histamine causing a 20% decrease in FEV(1) (PC(20) histamine) and PC(20) methacholine were determined before and at 1.5, 3, and 6 h after inhalation of 0.25 or 0.5 mg of terbutaline sulfate. The Turbuhaler delivered significantly more drug than did the pMDI (% of the nominal metered dose and 95% confidence interval): 20.8% (16.4 to 26.6%) and 16.9% (13.2 to 21.7%) versus 4.8% (3.8 to 6.1%) and 7.4% (5.8 to 9.5%), respectively. Average protection against histamine over 6 h was 0.66 (95% CI: 0.45 to 0.87) doubling concentrations (DC) after inhalation of 0.25 mg and 1.08 (95% CI: 0.87 to 1.29) DC after 0.5 mg terbutaline via pMDI, and 1.07 (95% CI: 0.87 to 1.29) DC after 0.25 mg and 1.24 (95% CI: 1.03 to 1.45) DC after 0.50 mg via Turbuhaler. Protection against methacholine was also dose- and device-dependent. The dose needed to obtain the same pulmonary deposition with the pMDI was 3.14 times greater than with the Turbuhaler, and that needed for the same protective effect was 2.1 and 3.2 times greater for histamine and methacholine, respectively. We conclude that pulmonary deposition of terbutaline was predictive of the clinical response.

The prognosis of pulmonary sarcoidosis in Finland and Hokkaido, Japan. A comparative five-year study of biopsy-proven cases.

BACKGROUND AND AIM OF THE STUDY: The frequency and clinical picture of sarcoidosis are different in Finland and Hokkaido, Japan. The aim of this study was to compare the normalisation rate of chest radiographic changes in patients with biopsy-proven sarcoidosis. METHOD: The chest radiographs of 437 Finnish and 457 Japanese patients were used and, for the purpose of this study, double-checked in order to make sure that the interpretations were identical. On a yearly basis the radiographs were classified as normalised, improved, unchanged or deteriorated. RESULTS: Normalisation of chest radiographs occurred in 73% of the Japanese and 40% of the Finnish patients. The difference between the two series was significant (p < 0.001). Gender, young age, presence or absence of symptoms or extrapulmonary lesions at diagnosis or treatment with corticosteroids did not influence the difference between the two series. Of the 191 Finnish and 309 Japanese patients with initial stage I disease a normal chest radiograph was obtained in 47% of the Finnish and 76% of the Japanese patients (p < 0.001), despite the fact that the Finnish series included patients with erythema nodosum, who had a 59% normalisation rate. Of the 186 Finnish and 125 Japanese patients with initial stage II disease, normalisation of the chest radiographs was seen in 36% of the Finnish and in 73% of the Japanese patients (p < 0.001). No difference in normalisation rate was seen between stage III patients. CONCLUSION: The prognosis of pulmonary sarcoidosis in Japanese patients in Hokkaido is significantly better than that in Finland defined as normalisation rate of the chest radiographs.

Familial sarcoidosis in Finland and Hokkaido, Japan--a comparative study.

Two or more cases of sarcoidosis in one family is not unusual. To compare the frequencies of familial sarcoidosis in Finland and Hokkaido, Japan, and to analyse the type of associations reported, we collected data on all patients visiting hospitals for sarcoidosis in 1984 in Finland (1378 patients) and Hokkaido (208 patients), including information about familial sarcoidosis. We also analysed the familial cases seen among 571 sarcoidosis patients diagnosed at the Mjölbolsta hospital in Finland from 1955 to 1987 and among 686 Japanese patients seen in Sapporo from 1964 to 1988. In 1984, 50 sarcoidosis patients visiting Finnish hospitals and nine sarcoidosis patients in Hokkaido reported as familial cases. Of the sarcoidosis patients seen in Finland at the Mjolbolsta hospital in 1955-1987, 27 had a family member with the same disease, while this number was 20 in the Sapporo hospital in 1964-1988. Those surveys give a prevalence of familial sarcoidosis in Finland of 3.6-4.7% and in Hokkaido of 2.9-4.3%. Among familial cases, the dominating relationships were sister-brother and mother-child relationships.

The mode of presentation of sarcoidosis in Finland and Hokkaido, Japan. A comparative analysis of 571 Finnish and 686 Japanese patients.

We compared the clinical picture of sarcoidosis in patients diagnosed at Mjölbolsta hospital in Finland in 1955-1987 with those diagnosed in Sapporo in 1964-1988. The female:male ratios showed a slight female predominance. The mean age (SD) at diagnosis was 41.5 (13.0) years at Mjölbolsta and 30.0 (15.4) years in Sapporo. In both series, half of the patients had been detected at mass x-ray surveys. The presenting symptoms varied considerably among the symptomatic patients. At Mjölbolsta hospital, 189 patients (33%) had cough, 21% fever, 21% general malaise, 18% dyspnoea, 18% erythema nodosum, 16% joint pain and only 27 patients (5%) had eye symptoms. In Sapporo, 245 patients (41%) had eye symptoms, 18 (4%) had enlarged peripheral lymph nodes, 14 (3%) had cough, 10 (2%) had fever. Erythema nodosum did not occur as a presenting symptom in Sapporo. The chest radiographs showed bilateral hilar lymphadenopathy (BHL, stage I) in 48% of the Mjölbolsta patients and in 57% of the Sapporo patients. Stage II lesions were seen in 39% and 20%, and stage III lesions in 12% and 5% respectively. Only 1% had a normal chest radiograph at Mjölbolsta hospital as compared with 18% in Sapporo. The Sapporo patients were more obstructive but the proportion of smokers was also higher. No difference in diffusion capacity was seen.

Effect of early vs late intervention with inhaled corticosteroids in asthma.

One hundred five consecutive patients with mild or moderate asthma not earlier treated with inhaled corticosteroids and with a need of an inhaled bronchodilator of three or more doses a week, and/or asthma symptoms during day or night, and/or peak expiratory flow (PEF) or FEV1 less than 75% of predicted normal values were given an inhaled corticosteroid for 2 years (budesonide delivered via an inspiratory flow-driven multidose dry powder inhaler [Turbuhaler]). According to duration of symptoms, they were divided into six groups; from a duration less than 6 months up to a duration more than 10 years. PEF and FEV1 were measured before and after treatment for 3 months, 1 year, and 2 years. In the groups of patients with a duration of symptoms less than 2 years, mean FEV1 and PEF were significantly higher at all time points as compared with the baseline and as compared with the groups of patients with a longer duration of asthma symptoms. The maximum effects were usually seen after 1 year's treatment with maintained control during the second year. A significant negative correlation was found between duration of symptoms and maximum increases in PEF (r = -0.34; p = 0.0006) and FEV1 (r = -0.32; p = 0.0012), a correlation remaining also after correcting for baseline airway function. No correlation was found between the age of the patients or earlier regular use of beta 2-agonists and improvements in airway function. The results give some evidence that early treatment of asthma with an inhaled steroid may prevent patients from developing chronic airway obstruction. They also support current asthma treatment guidelines advocating early introduction of inhaled anti-inflammatory drugs.

The frequency of sarcoidosis in Finland and Hokkaido, Japan. A comparative epidemiological study.

Finland and Hokkaido resemble each other; the four season climate with cold winters and cool summers is the same as is the frequency of tuberculosis. The size of the population is almost the same. From the 1984 Japanese nationwide sarcoidosis survey we got the data from Hokkaido (288 patients) in order to compare the information with similarly collected data in Finland from 1984 (1,378 patients). The crude prevalence of sarcoidosis was 28.2 per 100,000 in Finland and 3.7 per 100,000 in Hokkaido. The annual incidence was 11.4 per 100,000 in Finland and 1.0 per 100,000 in Hokkaido. The sex distribution was similar; 63% vs 67% women in Finland and Hokkaido, respectively. At diagnosis the Hokkaidoan patients were significantly younger. In Hokkaido more cases were detected via mass X-ray survey (43% vs 34%). Among symptomatic patients eye symptoms were more frequent in Hokkaido, whereas respiratory and joint symptoms and erythema nodosum were more frequent in Finland. Bilateral hilar lymphadenopathy (BHL) was equally distributed (82% vs 84% whereas parenchymal lesions were seen more often in Finland (49% vs 25%) as well as peripheral lymphadenopathy (16% vs 8%).

Comparison of terbutaline and placebo from a pressurised metered dose inhaler and a dry powder inhaler in a subgroup of patients with asthma.

BACKGROUND: Reversibility after administration of an inhaled bronchodilator is not always demonstrable in patients with asthma. Bronchodilator aerosol-induced bronchoconstriction has also been reported to occur in some patients. METHODS: Fifteen selected patients showing < 10% improvement in forced expiratory volume in one second (FEV1) when tested with four doses of salbutamol (0.1 mg/dose) or terbutaline (0.25 mg/dose) from a pressurised metered dose inhaler (MDI) participated in two randomised, double blind studies. They received 2.0 mg terbutaline (4 x 2 doses of 0.25 mg) or a corresponding placebo from an MDI connected to a 750 ml spacer, and 1.0 mg (2 x 0.5 mg) terbutaline or placebo from a multidose dry powder inhaler free of additives (Turbohaler). RESULTS: Inhalation of placebo MDI resulted in a mean (SD) decrease in FEV1 of 20.5 (14.1)% (range -42.9% to +2.6%). In 14 patients inhalation of 2.0 mg terbutaline MDI with spacer resulted in < 10% improvement (mean increase 3.1 (6.0)%). One mg of terbutaline via a Turbohaler resulted in improvements in FEV1 of > 15% in eight patients (mean increase 16.0 (9.7)%). The improvement was < 10% in four patients. Use of placebo Turbohaler did not affect airway calibre (mean change 0.2 (2.9)%). CONCLUSIONS: Additives of MDIs may cause bronchoconstriction in some patients with asthma. In these patients inhalation from a pressurised metered dose inhaler is more likely to decrease the bronchodilator response than inhalation from an additive-free inhaler. The frequency of this phenomenon is unknown.

Clinical efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI with volumatic spacer. A 2-year randomized study in 102 asthma patients.

A total of 102 patients had their asthma treatment with beclomethasone dipropionate (BDP) optimized in order to achieve the best possible control of symptoms. Thereafter, the BDP doses were gradually reduced over a 2-year period (1988-90) to the lowest possible without deterioration of their asthmatic condition. In the beginning of 1990, treatment was changed in 76 patients (group A) to the nearest possible dose of budesonide delivered via Turbuhaler. Twenty-six randomly selected patients (25% of the study population; group B) continued treatment with BDP. In both groups, dose reductions were tried during 1990-2 every third month as long as the patients remained symptom-free and without significant decreases in FEV1 or PEF. In group A, the maintenance dose could be reduced from 1003.9 +/- 325.4 micrograms BDP (mean +/- SD) to 602.9 +/- 454.4 micrograms budesonide Turbuhaler (P < 0.001). In group B, no significant dose reduction was possible; the mean dose was +/- SD 1067.3 +/- 36.6 micrograms in 1990, and 1019.2 +/- 324.7 micrograms in 1992. The results indicate that, in efficacy, 0.6 mg budesonide Turbuhaler corresponds to approximately 1.0 mg BDP with volumatic spacer. This difference is probably due to an improved pulmonary delivery of budesonide with Turbuhaler.

Local side-effects during 4-year treatment with inhaled corticosteroids--a comparison between pressurized metered-dose inhalers and Turbuhaler.

Local side-effects, such as hoarseness and oropharyngeal candidiasis, are often seen during treatment of patients with inhaled corticosteroids (ICS). We investigated whether changing from pressurized metered-dose inhalers (pMDI) to Turbuhaler influenced the type and frequency of local side-effects. Local side-effects were recorded for a 2-year period in which 154 patients used ICS pMDI with a spacer device. They were followed for an equally long period of time (26.2 +/- 5.7 months) while using Turbuhaler, as were 90 patients who received Turbuhaler as their first ICS preparation. After inhalation, all patients rinsed out their mouths with water. In experienced pMDI-users, the frequency of local side-effects decreased from 21% to 6%. The reduction was due to a lower incidence of hoarseness. Candidiasis or hoarseness was not seen in patients given Turbuhaler as their first ICS device. Our fear of an increased incidence of local side-effects when giving ICS in Turbuhaler was unwarranted.

Inhaled budesonide for maintenance treatment of pulmonary sarcoidosis.

Forty-seven patients with pulmonary sarcoidosis stage II-III, fulfilling clinical indications for starting treatment with corticosteroids, received oral methylprednisolone for 8 weeks in gradually decreasing doses (starting dose 48 mg per day). From week 5 onwards, they also received inhaled budesonide, 1.6 mg daily. Treatment was continued for 18 months and all patients have been followed for at least 3 years. At 18 months treatment could be discontinued in 38 patients, who had used individually adjusted doses of budesonide depending on the clinical response (reduced doses in 14, initial dose in 16, and increased doses in 8 patients). Budesonide treatment alone was satisfactory in 31 of these 38 cases. An additional seven patients could stop treatment after receiving supplementary courses of oral steroids for 3-12 months. Treatment is ongoing in 9 patients in which 6 have extrapulmonary manifestations requiring oral steroids. The chest radiograph became normal in 22 patients and improved in 14. Significant improvements were noted in FVC and DLco in relation to predicted normal values. Serum ACE, lysozyme and beta 2-microglobulin values decreased significantly. Transient cough was seen in 5 and hoarseness in 3 patients. No systemic side-effects were noted; one patient taking 2.4 mg budesonide daily had a plasma cortisol value below the normal range. Inhaled budesonide seems to offer an effective and safe alternative to oral steroids for long-term maintenance treatment of patients with pulmonary sarcoidosis.