Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis

doi:10.1016/S0022-3476(96)70407-9

The Journal of Pediatrics

Volume 128, Issue 2, February 1996, Pages 271-274

Presented in part at the Annual Congress of the European Respiratory Society in Nice, France, Oct. 1-5, 1994, and at the Annual Congress of the Society of Paediatric Pneumology in Davos, Switzerland, March 16-18, 1995.

https://doi.org/10.1016/S0022-3476(96)70407-9 Get rights and content

Abstract

OBJECTIVE: To determine the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis. STUDY DESIGN: We report a pilot study of 49 patients with cystic fibrosis and moderate to severe bronchial obstruction (forced expiratory volume in 1 second ≤55% of the predicted value); 25 patients were given inhaled corticosteroids for 30 days (1500 μg of beclomethasone via spacer), and 24 patients had the same standard treatment but no inhaled corticosteroids. RESULTS: Forced vital capacity, forced expiratory volume in 1 second, and airway resistance showed significant improvement in both study groups, but thoracic gas volume and the diffusion capacity of the lung for carbon monoxide improved significantly only in the group given inhaled corticosteroids. When concomitant medications were taken into account, analysis of variance confirmed a significant effect of inhaled corticosteroids on the improvement of thoracic gas volume. CONCLUSION: Inhaled corticosteroids in combination with standard treatment can contribute to the improvement of lung function in patients with cystic fibrosis and moderate to severe bronchial obstruction. Our preliminary data seem encouraging enough to warrant a multicenter, long-term, blind control study. (J PEDIATR 1996;128:271-4)

Section snippets

METHODS

In our retrospective analysis of ICS, the mean FEV₁ was 41% (SD = 14%) of the predicted values, and the magnitude of improvement achieved during the study period of 34.5 ± 12.5 days was 12.4%.⁵ To demonstrate the same amount of improvement in FEV₁ on a significance level of 5%, we had to enroll 17 patients in each arm of the study; 25 patients were required to reach a significance level of 2%. Fifty patients admitted to our rehabilitation center in Davos, Switzerland, were informed about the

RESULTS

Characteristics of both study groups—such as age, severity of the disease as shown by Shwachman score⁶ or by total serum concentration of IgG,⁹ or atopic and infectious status (data not shown)—were not significantly different between the groups (p >0.05). The same applies to bacterial colonization and antibiotic treatment regimens (data not shown).

Lung function test results on entry are summarized in the Table. There was no significant difference in any measurement between the groups (p >0.05).

DISCUSSION

These preliminary data from a controlled study of ICS in the treatment of patients with CF show that, for a limited time, topically administered steroids significantly improved TGV and CO diffusion. The improvement of bronchial obstruction and pulmonary hyperinflation was accompanied by significantly better CO diffusion, suggesting a better peripheral ventilation/perfusion ratio.

Our study has limitations, mainly the short duration of therapy, the lack of standardization of other therapy, the

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Effect of inhaled corticosteroids on lung function in cystic fibrosis patients [Abstract]
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Cystic fibrosis (CF) lung disease is characterized by aggressive neutrophil-dominated inflammation mediated in large part by neutrophil elastase (NE), an omnivorous protease released by activated or disintegrating neutrophils and a key therapeutic target. To date, several short-term studies have shown that anti-NE compounds can inhibit NE and have anti-inflammatory effects. However, progression to large-scale or multicenter clinical trials has been hampered by the fact that the current gold standard methodology of evaluating airway NE inhibition, bronchoalveolar lavage (BAL), is invasive, difficult to standardize across sites and excludes those with severe lung disease. Attempts to utilize sputum that is either spontaneously expectorated (SS) or induced (IS) have been hindered by poor reproducibility, often due to the various processing methods employed. In this study, we evaluate TEmperature-controlled Two-step Rapid Isolation of Sputum (TETRIS), a specialized method for the acquisition and processing of SS and IS. Using TETRIS, we show for the first time that NE activity and cytokine levels are comparable in BAL, SS and IS samples taken from the same people with CF (PWCF) on the same day once this protocol is used. We correlate biomarkers in TETRIS-processed IS and clinical outcome measures including FEV₁, and show stability and reproducible inhibition of NE over time in IS processed by TETRIS. The data offer a tremendous opportunity to evaluate prognosis and therapeutic interventions in CF and to study the full spectrum of people with PWCF, many of whom have been excluded from previous studies due to being unfit for BAL or unable to expectorate sputum.
The Epidemiology and Management of Lung Diseases in Sickle Cell Disease: Lessons Learned from Acute and Chronic Lung Disease in Cystic Fibrosis
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Despite the challenging clinical diagnosis of asthma in individuals with CF, multiple studies have demonstrated the benefit of asthma therapies in the CF population. Several randomized controlled trials have been performed to examine the impact of inhaled bronchodilators,28,29 montelukast,30 inhaled glucocorticoids,31–33 and systemic glucocorticoids34,35 on individuals with CF without a focus on distinguishing those with a concomitant asthma diagnosis or not. The definition of asthma in SCD often relies on whether asthma medication has been prescribed.
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2014, Archives de Pediatrie
La justification de l’utilisation des corticoïdes inhalés (CI) n’est pas clairement établie dans la mucoviscidose.
Établir un consensus formalisé pour la prescription des CI dans cette pathologie.
Application de la méthode Delphi, concernant 5 champs thématiques : indications, non-indications, posologie, précautions d’emploi et suivi d’un traitement par CI.
Trente sur quarante-neuf (61 %) des centres de ressources et de compétences pour la mucoviscidose (CRCM) de France ont participé à la démarche, qui a compris 3 tours. Les experts ont validé l’indication des CI en cas de manifestations pulmonaires avec sibilants, d’antécédents personnels ou familiaux d’atopie ou de signes d’hyperréactivité bronchique. En revanche, les CI ne sont pas indiqués en première intention du traitement de l’aspergillose broncho-pulmonaire allergique. Un fort consensus a également été obtenu sur les doses qui doivent être celles utilisées dans l’asthme, en recherchant la dose minimale efficace, et adaptées au contrôle des symptômes. Il n’est pas recommandé d’accroître le rythme de surveillance de la flore bactérienne et mycologique des crachats des patients, ni de réaliser de surveillance ophtalmologique pour la survenue de cataracte. Par contre, en cas de prise prolongée (plus de 6 mois) de doses élevées, il est recommandé de surveiller l’ostéodensitométrie, ainsi que l’axe corticotrope lorsque le patient est sous traitement concomitant d’itraconazole.
Ce consensus définit ainsi le périmètre de prescription des CI dans la mucoviscidose, dans le but de limiter leur prescription (jusqu’à la preuve du contraire).
The conditions for the prescription of inhaled steroids (ISs) in cystic fibrosis (CF) are not well established.
To propose a formalized consensus agreement regarding the prescription of ISs in this disease.
Application of the Delphi method in five thematic fields: indications, non-indications, dosage, precautions for use, and treatment follow-up.
Thirty of forty-nine (61 %) reference CF centers in France participated in the process, which comprised three rounds. Experts strongly agreed that ISs are indicated in the presence of pulmonary manifestations with wheezing, personal history of atopy, and/or bronchial hyper-responsiveness. In contrast, ISs are not indicated as first-line therapy for allergic bronchopulmonary aspergillosis. Strong agreement was reached regarding the daily dose of ISs, which should be similar to what is given in asthma and adapted to control symptoms so as to prescribe the smallest possible dose. Increasing the frequency of bacterial and fungal sputum analyses and eye (cataract) assessments was not deemed necessary. However, in case of prolonged (> 6 months) use of high-dose ISs, monitoring bone mineral density and the hypothalamic-pituitary-adrenal axis, in particular if itraconazole is concomitantly prescribed, was recommended.
This consensus statement defines a perimeter for the prescription of ISs in CF, with the aim of limiting their prescription (until new data are available).
Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus
2009, Journal of Cystic Fibrosis
In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics, mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we address the subject of testing new devices before market introduction.
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^☆: From Alpine Children's Hospital, Davos Platz, Switzerland

^☆☆: Reprint requests: Wilfried H. Nikolaizik, MD, Alpine Children's Hospital, Scalettastr. 5, CH-7270 Davos Platz, Switzerland.

^★: 0022-3476/96/$5.00 + 0 9/25/69629

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Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis☆,☆☆,★

Abstract

Section snippets

METHODS

RESULTS

DISCUSSION

J Pediatr

J Pediatr

Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis

Lancet

Risks of alternate-day prednisone in patients with cystic fibrosis

Pediatrics

Endocrine and lung function in asthmatic children on inhaled corticosteroids

Am J Respir Crit Care Med

Effect of inhaled corticosteroids on lung function in cystic fibrosis patients [Abstract]

Eur Respir J