pulmicort and Sarcoidosis

The aim of this investigation was to compare inhaled budesonide vs oral prednisone in the maintenance phase treatment of pulmonary sarcoidosis. Double-blind controlled study was performed in 40 patients with stage II or III pulmonary sarcoidosis. After initial systemic 6 weeks treatment with prednisone (40 reduced to 20 mg daily) patients were allocated either to systematically (P) or topically (B) treated group. P patients continued with 10 mg prednisone daily, B patients were given inhaled budesonide 1.6 mg daily. The progress of treatment was assessed by serial radiography, spirometry, serum ACE activity and plasma cortisol levels. All patients completed the 12 months treatment. Using a numerical score to assess changes on the chest radiograms P patients improved by 1.7 +/- 0.66 points; B patients improved by 1.15 +/- 0.81 points. Spirometric changes were insignificant. Serum ACE fell from 107 +/- 51 U/L in the P group and 92 +/- 40 U/L in the B group to 46 +/- 11 U/L and 38 +/- 21 U/L respectively during the initial phase of treatment. In the maintenance phase ACE levels remained lower than initial ones in both groups. Morning cortisol plasma levels studied in 10 patients (5 in each group) decreased significantly during the initial phase. Thereafter cortisol levels remained low in the P patients returning to the lower limit of normal values in the B patients. We conclude that inhaled budesonide may be a safe and effective alternative to oral steroids in the maintenance treatment of pulmonary sarcoidosis especially in the early, stage II, disease.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Humans; Lung Diseases; Male; Middle Aged; Placebos; Prednisone; Pregnenediones; Respiration; Sarcoidosis; Time Factors

We investigated the effect of inhaled corticosteroids on the phenotypes and functional capacity of macrophages obtained by bronchoalveolar lavage from patients with pulmonary sarcoidosis. The results were correlated with clinical status and therapeutic efficacy. Ten symptomatic sarcoid patients (previously untreated) with radiological parenchymal shadowing and abnormal pulmonary function received inhaled budesonide, 800 micrograms m twice daily via a Nebuhaler for 16 weeks. A placebo group included ten healthy volunteers and five sarcoid patients with similar features to the treated group. Drug distribution studies showed that 10% of the inhaled drug was deposited in the alveolar region. All ten treated sarcoid patients had symptomatic relief with no adverse effects. Three of these ten patients had significant resolution of their radiological shadowing. No significant difference in pulmonary function was observed. At the cellular level, a significant decrease in lavage lymphocytosis was seen after 16 weeks, during which time there was a concomitant change in the phenotype and functional characteristics of the alveolar macrophage population. No similar changes were observed in the placebo group. Our results suggest that inhaled budesonide can modulate the aberrant immunological reactions existent in the lung in pulmonary sarcoidosis, and produce concomitant symptomatic relief with no side effects. It is postulated that this effect may occur through action on the local alveolar macrophage population.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Budesonide; Female; Humans; Lung Diseases; Lymphocyte Culture Test, Mixed; Macrophages; Male; Phenotype; Pregnenediones; Sarcoidosis

In a randomized, double-blind study 19 patients with newly-detected pulmonary sarcoidosis were treated with either inhaled budesonide, 800 micrograms twice daily (n = 9), or placebo (n = 10) for 8-10 weeks. Before and after treatment, chest roentgenograms, lung function tests, bronchoalveolar lavage (BAL) and biochemical tests were performed. Angiotensin converting enzyme (ACE) activity and beta2-microglobulin (beta 2M) concentrations were measured in serum. The same tests, as well as albumin and hyaluronan were measured in the BAL-fluid. The total cell number in BAL-fluid, differential counts and lymphocyte subpopulations were determined (total T- and B-lymphocytes, T-helper/inducer (OKT-4) and T-suppressor/cytotoxic (OKT-8) lymphocytes). No significant changes in chest roentgenograms or lung function tests were observed during the short study time. However, a decrease in serum ACE (p less than 0.1) and beta 2 M (p less than 0.05) as well as in BAL-hyaluronan (p less than 0.01) was found in the budesonide-treated patients as well as a decrease in the percentage of BAL T-lymphocytes (p less than 0.05) and the T4/T8 ratio (p less than 0.1). No significant changes were seen in the placebo group. The findings suggest that treatment with inhaled budesonide influences biochemical and cellular findings in patients with early sarcoidosis in the same way as treatment with systemic corticosteroids. The results may also explain clinical effects seen in sarcoidosis patients treated with inhaled corticosteroids. However, further studies are required to determine the long-term clinical benefits of inhaled steroids in pulmonary sarcoidosis.

Topics: Administration, Inhalation; Adult; beta 2-Microglobulin; Bronchoalveolar Lavage Fluid; Budesonide; Clinical Trials as Topic; Double-Blind Method; Female; Glucocorticoids; Humans; Hyaluronic Acid; Lung; Lung Diseases; Male; Middle Aged; Peptidyl-Dipeptidase A; Pregnenediones; Radiography; Random Allocation; Sarcoidosis

Corticosteroids are the drugs of choice for treatment of sarcoidosis. Frequently the pulmonary parenchymal lesions with impaired lung function represent the indication for starting treatment. Oral glucocorticosteroids may cause systemic side-effects and therefore treatment is often started too late in the hope of a spontaneous recovery. With the introduction of the locally potent glucocorticosteroid budesonide (Pulmicort) the active alveolitis as well as the pulmonary parenchymal lesions can be treated with only inhaled steroids and without causing systemic effects. If wanted, treatment of pulmonary sarcoidosis can therefore be started early without waiting for a possible spontaneous improvement. Systemic sarcoidosis outside the lungs cannot, however, be treated with locally administered drugs. The most rapid improvement of the pulmonary manifestations is achieved if an initial combination of oral and inhaled steroids is used for 2-3 months. Thereafter the long-term maintenance treatment can be given with only inhaled budesonide.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Animals; Budesonide; Glucocorticoids; Humans; Lung Diseases; Pregnenediones; Sarcoidosis

Twenty patients with active sarcoidosis (increased serum ACE activity) and progressive pulmonary disease (stages 2-3) were treated with inhaled budesonide instead of with oral glucocorticosteroids in an open clinical study. Results after an 18-month treatment are reported. A general improvement in chest roentgenograms and FVC was noted. Serum ACE activity was normalized. The results indicate that pulmonary manifestations of sarcoidosis can be treated with the inhaled steroid, budesonide. In this way the risk of systemic side effects is considerably reduced. The final place of inhaled budesonide in the treatment of sarcoidosis must be determined via placebo-controlled and comparative, double-blinded clinical studies in larger series of patients.

Topics: Adult; Aged; Budesonide; Drug Evaluation; Female; Glucocorticoids; Humans; Lung; Lung Diseases; Male; Middle Aged; Peptidyl-Dipeptidase A; Pregnenediones; Radiography; Respiratory Therapy; Sarcoidosis; Time Factors; Vital Capacity