A double-blind, randomized study of sodium cromoglycate versus placebo in patients with cystic fibrosis and bronchial hyperreactivity

doi:10.1016/0091-6749(90)90106-E

Journal of Allergy and Clinical Immunology

Volume 85, Issue 3, March 1990, Pages 649-654

https://doi.org/10.1016/0091-6749(90)90106-E Get rights and content

Abstract

To evaluate the effects of sodium cromoglycate (SCG) on patients with cystic fibrosis (CF) and with bronchial hyperreactivity, a long-term, double-blind, placebo-controlled, crossover study was performed. Fourteen patients with CF and without asthma (aged 7 to 29 years) and with bronchial hyperreactivity entered the study. Each patient received 8 weeks of 1% SCG nebulizer solution three to four times daily and 8 weeks of placebo. Seven patients received the treatment in the order SCG / placebo and seven patients in the reverse order. Evaluation of SCG effect was performed every 4 to 8 weeks by (1) clinical assessment of symptoms, (2) clinician and patient/parent opinion, (3) pulmonary function tests, and (4) methacholine provocation tests. After two patients were withdrawal for lack of cooperation, the results were evaluated for treatment effect (SCG versus placebo), period effect (whether SCG was administered first or last), or combination of both. No significant difference was found for these parameters for the clinical assessment of symptoms, the patient/parent and clinician opinion, their subjective preferences, the methacholine challenges, or the pulmonary function tests. The study did not demonstrate any benefit from the use of SCG in patients with CF and with bronchial hyperreactivity and does not support the routine use of SCG in patients with CF.

References (26)

VJ Derbes et al.
Intrinsic (nonallergic) bronchial asthma as a manifestation of fibrocystic disease of the pancreas
J Allergy Clin Immunol
(1957)
I Mitchell et al.
Bronchial hyperreactivity in cystic fibrosis and asthma
J Pediatr
(1978)
LI Landau et al.
The variable effect of a bronchodilating agent on pulmonary function in cystic fibrosis
J Pediatr
(1973)
S Godfrey et al.
The place of cromolyn sodium in the long-term management of childhood asthma based on a 3 to 5 year follow-up
J Pediatr
(1975)
H Chai et al.
Standardization of bronchial inhalation challenge procedures
J Allergy Clin Immunol
(1975)
MP Griffin et al.
Short-and long-term effects of cromolyn sodium on the airway reactivity of asthmatics
J Allergy Clin Immunol
(1983)
JL Black et al.
Cromolyn sodium inhibits the increased responsiveness to methacholine that follows ultrasonically nebulized water challenge in patients with asthma
J Allergy Clin Immunol
(1987)
CM Smith et al.
Methacholine responsiveness increases after ultrasonically nebulized water but not after ultrasonically nebulized hypertonic saline in patients with asthma
J Allergy Clin Immunol
(1987)
CM Mellis et al.
Bronchial reactivity in cystic fibrosis
Pediatrics
(1978)
LP Ormerod et al.
Reversible airway obstruction in cystic fibrosis
Thorax
(1980)

NL Hordvik et al.

A longitudinal study of bronchodilator responsiveness in cystic fibrosis

Am Rev Respir Dis

(1985)

JO Warner et al.

Association of cystic fibrosis with allergy

Arch Dis Child

(1976)

CP Warren et al.

Cystic fibrosis—immunological reactions to A. fumigatus and common allergens

Clin Allergy

(1975)

Cited by (14)

Pharmaceutical and biotechnological aerosols for cystic fibrosis therapy
2002, Advanced Drug Delivery Reviews
The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis
1995, Respiratory Medicine
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 μg 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 μg 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.
Cystic fibrosis
1993, Disease-a-Month
Cystic fibrosis, an autosomal recessive disorder, is the most common genetic disease of Caucasians. One in 25 Caucasians are carriers of the gene. The gene is found far less commonly in other races. There are over 230 different alleles of the gene, located on the 7th chromosome. The gene encodes for a membrane protein that functions as an ion channel. The survival of cystic fibrosis patients has been gradually increasing, with a mean survival in 1990 of 28 years. If the current trend of improved survival continues, it is estimated that half of cystic fibrosis patients will be over 18 years old by 1996. Disease is found in many organs including the lungs, sinuses, pancreas, gastrointestinal tract, hepatobiliary system, sweat glands and reproductive tract. The majority of patients die of pulmonary disease. The airways become chronically colonized with bacteria that cannot be eradicated, leading to bronchitis, bronchiectasis, and finally, pulmonary fibrosis with respiratory failure. The pulmonary disease may be complicated by massive hemoptysis and pneumothorax. Patient survival rates have increased because of antibiotic therapy and improved nutrition with pancreatic enzyme replacements. New treatments for the pulmonary disease are under clinical trial and include antiproteases, amiloride, a sodium channel blocker, and DNase. The insertion of the normal cystic fibrosis allele into an animal model using a modified adenovirus with effective transcription suggests that gene therapy may be possible in the future, but safety and technical problems have to be addressed.
Complicating features of asthma
1992, Pediatric Clinics of North America
Inhaled bronchodilators for cystic fibrosis
2016, Cochrane Database of Systematic Reviews
Cystic fibrosis pulmonary guidelines: Chronic medications for maintenance of lung health
2007, American Journal of Respiratory and Critical Care Medicine

View all citing articles on Scopus

^☆: Supported by a grant from Fisons Pharmaceutical, Loughborough, Leicestershire, England.

^∗: From the Department of Pediatrics, University of California, San Francisco, Calif.

^∗∗: From the Riley Children's Hospital, Indianapolis, Ind.

^∗∗∗: Children's Hospital of Northern California, Oakland, Calif.

View full text

Original articleA double-blind, randomized study of sodium cromoglycate versus placebo in patients with cystic fibrosis and bronchial hyperreactivity☆

Abstract

J Allergy Clin Immunol

J Pediatr

J Pediatr

J Pediatr

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Bronchial reactivity in cystic fibrosis

Pediatrics

Reversible airway obstruction in cystic fibrosis

Thorax

A longitudinal study of bronchodilator responsiveness in cystic fibrosis

Am Rev Respir Dis

Association of cystic fibrosis with allergy

Arch Dis Child

Cystic fibrosis—immunological reactions to A. fumigatus and common allergens

Clin Allergy

Original article
A double-blind, randomized study of sodium cromoglycate versus placebo in patients with cystic fibrosis and bronchial hyperreactivity☆