The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis

Abstract

Bronchial hyperresponsiveness is present in 40-60% of adult patients with cystic fibrosis (CF). Drugs which alter airway hyperresponsiveness have not yet been studied in CF. In this randomized placebo-controlled study, we investigated the effects of an inhaled corticosteroid, budesonide, on lung function and bronchial hyperresponsiveness in adult CF patients, with proven bronchial hyperresponsiveness to histamine. Twelve patients were treated with budesonide, 1600 micrograms day-1, and with placebo during two periods of 6 weeks in a randomized, double-blind, cross-over study. Drug effects were assessed with regard to bronchial hyperresponsiveness to histamine, spirometry and clinical symptom scores. After treatment with budesonide, no significant differences in spirometry were seen, however, bronchial hyperresponsiveness to histamine significantly improved as compared to baseline. Fifty-eight percent of the patients showed at least one doubling-dose increase in PC20 histamine. Daily symptom scores showed small, but statistically significant, improvements in dyspnoea and cough after budesonide treatment. There is increasing evidence suggesting that excessive inflammatory responses contribute to the pulmonary damage that characterizes CF. Treatment with oral corticosteroids improved the clinical course of selected CF patients, but was associated with unacceptable adverse effects. We conclude that daily inhalation of 1600 micrograms day-1 budesonide for 6 weeks induced a small, but significant, improvement in bronchial hyperresponsiveness to histamine, and symptoms of cough and dyspnoea in adult CF patients. Longer observations are needed to establish whether inhaled corticosteroids improve the long term outcome of CF.

Deve-se extrapolar o tratamento de bronquiectasias em pacientes com fibrose cística para aqueles com bronquiectasias de outras etiologias?

“…Despite its potential benefit in terms of reducing the amount of secretion produced in patients with bronchiectasis and improving the quality of life measured by means of questionnaires, the use of inhaled corticosteroids did not reduce the number of exacerbations and the drop in pulmonary function. (21,22) At our center, the use of inhaled corticosteroids has more individualized indications, such as in patients with good response to the bronchodilator in spirometry and who present a large quantity of pulmonary secretion. The easier access to combined treatment (long-effect bronchodilators + inhaled corticosteroids), as a substitute for the use of bronchodilators in isolation, is also a factor that might have contributed to the higher prevalence of inhaled corticosteroid use in Brazil.…”

Bronchial Hyperreactivity Related to Inhalation Therapy in Cystic Fibrosis Patients

“…Similarly, early-life infection with respiratory syncytial virus in the general population is suggested to be one of the most important risk factors for the development of childhood asthma by deregulating local immunity [30]. In addition, Van Haren et al demonstrated in a placebo-controlled trial that treatment with inhaled corticosteroids decreases BHR in adult patients with CF, supporting the hypothesis that chronic inflammation can lead to the development of BHR [25]. Third, the distribution of inhaled aerosol throughout the respiratory tract varies depending on particle size, inspiratory flow rate, and total lung resistance [16].…”

“…Estimates are that about half of the CF patients demonstrate significant airway narrowing upon administration of these pharmacological agents [8,11,17,[19][20][21][22][23][24][25][26]. According to Weinberger et al, cohort studies support the presence of two types of airway reactivity in CF: (1) CF patients with concomitant clinical asthma who have BHR in response to metacholine, histamine and exercise; and (2) BHR in CF patients without concomitant clinical asthma [8,19,22,24,25]. The latter have BHR which differs from what is seen in asthma.…”

“…Although BHR is a functional characteristic of asthma, the etiology of BHR in CF is considered multifactorial and different hypotheses about the etiology of BHR in CF have been proposed (Figure 2) [8,[16][17][18][19]21,[23][24][25] Some authors suggest BHR occurs secondary to underlying airway disease in CF [16,20,21] others suggest it is a separate condition that occurs more commonly in CF, [8,22] while a third group believes BHR is the result of both mechanisms [8,19,23,24]. Three main explanations have been suggested to support the hypothesis of BHR occurring secondary to underlying airway disease, i.e.…”

Effect of inhaled steroids on clinical and inflammatoryparameters in children with cystic fibrosis

“…However, the efficacy and safety of inhaled corticosteroids (ICSs) are still controversial. Some studies suggest that ICS therapy in CF may improve lung function, reduce bronchial hyperreactivity (BHR), improve symptoms like cough and dyspnea, and reduce airway inflammation (7)(8)(9). In contrast, some studies did not show any improvement in clinical status or lung function (10,11).…”