Effects of prednisone on eosinophilic bronchitis in asthma:
               a systematic review and meta-analysis

Sakae, Thiago Mamôru; Maurici, Rosemeri; Trevisol, Daisson José; Pizzichini, Marcia Margaret Menezes; Pizzichini, Emílio

doi:10.1590/S1806-37132014000500012

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Jornal Brasileiro de Pneumologia

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META-ANALYSIS • J. bras. pneumol. 40 (5) • Sep-Oct 2014 • https://doi.org/10.1590/S1806-37132014000500012 copy

Effects of prednisone on eosinophilic bronchitis in asthma: a systematic review and meta-analysis^* * Study carried out under the auspices of the Graduate Program in Medical Sciences, Federal University of Santa Catarina, Florianópolis, Brazil. ,^ A versão completa em português deste artigo está disponível em www.jornaldepneumologia.com.br

Authorship SCIMAGO INSTITUTIONS RANKINGS

OBJECTIVE:

To evaluate the effect size of oral corticosteroid treatment on eosinophilic bronchitis in asthma, through systematic review and meta-analysis.

METHODS:

We systematically reviewed articles in the Medline, Cochrane Controlled Trials Register, EMBASE, and LILACS databases. We selected studies meeting the following criteria: comparing at least two groups or time points (prednisone vs. control, prednisone vs. another drug, or pre- vs. post-treatment with prednisone); and evaluating parameters before and after prednisone use, including values for sputum eosinophils, sputum eosinophil cationic protein (ECP), and sputum IL-5-with or without values for post-bronchodilator FEV₁-with corresponding 95% CIs or with sufficient data for calculation. The independent variables were the use, dose, and duration of prednisone treatment. The outcomes evaluated were sputum eosinophils, IL-5, and ECP, as well as post-bronchodilator FEV₁.

RESULTS:

The pooled analysis of the pre- vs. post-treatment data revealed a significant mean reduction in sputum eosinophils (↓8.18%; 95% CI: 7.69-8.67; p < 0.001), sputum IL-5 (↓83.64 pg/mL; 95% CI: 52.45-114.83; p < 0.001), and sputum ECP (↓267.60 µg/L; 95% CI: 244.57-290.63; p < 0.0001), as well as a significant mean increase in post-bronchodilator FEV₁ (↑8.09%; 95% CI: 5.35-10.83; p < 0.001).

CONCLUSIONS:

In patients with moderate-to-severe eosinophilic bronchitis, treatment with prednisone caused a significant reduction in sputum eosinophil counts, as well as in the sputum levels of IL-5 and ECP. This reduction in the inflammatory response was accompanied by a significant increase in post-bronchodilator FEV₁.

Meta-analysis; Bronchitis; Asthma; Pulmonary eosinophilia; Evidence-based medicine; Prednisone

Reference	Characteristics of the study	Treatment	Pre-treatment vs. post-treatment
Baigelman et al.⁽³⁰⁾	Design: observational	Drug: prednisone	Sputum eosinophils, mean ± SD: 26.0 ± 19.0% vs. 8.0 ± 5.0%
	Sample: 11 asthma patients (3 males and 8 females; 29-60 years of age) followed for at least 4 years	Dose: 80 mg/day	Sputum ECP: [not measured]
		Dose: 80 mg/day	post-bronchodilator FEV₁, mean ± SD: 1.03 ± 0.41 L vs. 1.32 ± 0.51 L
	Profile: asthma exacerbation	Duration: 3 days	IL-5: [not measured]
Claman et al.⁽³¹⁾	Design: randomized controlled trial
	Sample: 24 asthma patients—oral prednisone group (n = 12, 7 males and 5 females) and placebo group (n = 12, 6 males and 6 females)—excluding patients having used inhaled or oral corticosteroids in the last 6 weeks, having had an upper respiratory infection in the last 6 weeks, and having a smoking history of > 10 pack-years	Drug: oral prednisone	Sputum eosinophils, mean ± SE: 14.1 ± 5.0% vs. 1.8 ± 0.8%
		Dose: 0.5 mg/kg per day	Sputum ECP, mean ± SE: 325 ± 131 µg/mL vs. 144 ± 84 µg/mL
	Profile: asthma exacerbation	Duration: 6 days	post-bronchodilator FEV₁, mean ± SD: 88 ± 5.2% vs. 91 ± 4.87%
	Profile: asthma exacerbation	Duration: 6 days	IL-5: [not measured]
Keatings et al.⁽³⁴⁾	Design: single-blind crossover study	Drug: prednisolone	Sputum eosinophils, mean ± SD: 6.66 ± 0.98% vs. 0.99 ± 0.25%
	Design: single-blind crossover study	Drug: prednisolone	Sputum ECP, mean ± SD: 687.0 ± 87.0 µg/L vs. 80.2 ± 14.2 µg/L
	Sample: 15 COPD patients (excluded from this meta-analysis) and 11 patients with mild atopic asthma (1 excluded; 10 included for analysis; mean age 29.8 ± 3.4 years)	Dose: 30 mg/day
		Duration: 2 weeks	post-bronchodilator FEV₁:
	Profile: stable asthma		-in %, mean ± SD: 95.9 ± 5.7% vs. [not described]
			-in L, mean ± SE: [not described] vs. 3.92 ± 0.32 L
			IL-5: [not measured]
Pizzichini et al.⁽⁸⁾	Design: observational	Drug: prednisone	Sputum eosinophils, mean ± SD: 17.6 ± 10.0% vs. 0.89 ± 0.90%
	Sample: 10 asthma patients	Dose: 30 mg/day for 5 days, tapered to zero by day 10	Sputum ECP, mean ± SD: 5,338.4 ± 6690.7 µg/L vs. 985.5 ± 1311.0 µg/L
	Profile: asthma exacerbation	Duration: 10 days	post-bronchodilator FEV₁, mean ± SD: 1.5 ± 0.3 L vs. 2.5 ± 0.5 L
	Profile: asthma exacerbation	Duration: 10 days	IL-5, mean ± SD: 201 ± 128 pg/mL vs. 0.0 ± 55.6 pg/mL
Pizzichini et al.⁽¹⁰⁾	Design: observational	Drug: prednisone	Sputum eosinophils, mean ± SD: 16.3 ± 32.3% vs. 0.0 ± 0.5%
	Sample: 8 patients with prednisone-dependent asthma; >12% variability in FEV₁, baseline mean, 18.5% (range, 13-27%)	Dose: 30 mg/day	Sputum ECP, mean ± SD: 7480 ± 5240 µg/L vs. 700 ± 784 µg/L
	Profile: severe asthma	Duration: 7 days	post-bronchodilator FEV₁, mean ± SD: 55.7 ± 6.84% vs. 80.0 ± 15.91%
	Profile: severe asthma	Duration: 7 days	IL-5, mean ± SD: 66.5 ± 150 pg/mL vs. 44.1 ± 86 pg/mL
Di Franco et al.⁽³²⁾	Design: randomized controlled trial	Drug: prednisone	Sputum eosinophils: 52.0% [no SD or SE] vs. 11.0% [no SD or SE]
	Sample: 40 adult nonsmokers (9 males and 31 females; mean age, 45 ± 13 years; 3 excluded), in two arms—fluticasone (1,000 µg/day; n = 18) and prednisone (n = 19)	Dose: 40 mg/day, tapered to 10 mg/day by reducing the dose by 5 mg every other day	Sputum ECP: 904 µg/L [no SD or SE] vs. [not described]
	Profile: asthma exacerbation	Duration: 6 days	post-bronchodilator FEV₁, mean ± SD: 51.5 ± 14.4% vs. 83.6 ± 21.1%
	Profile: asthma exacerbation	Duration: 6 days	IL-5: [not measured]
Scheicher et al.⁽³³⁾	Design: controlled observational	Drug: oral prednisone	-
	Sample: 51 subjects—21 normal subjects and 30 patients with asthma (13 males and 17 females; mean age, 41 years), 9 of whom were steroid-naïve—the 9 steroid-naïve patients receiving oral prednisone and being evaluated before and after the treatment	Dose: 40 mg/day
	Profile: stable asthma	Duration: 14 days
Dente et al.⁽²⁹⁾	Design: randomized controlled trial	Drug: oral prednisone	-
	Sample: 59 patients with severe refractory asthma, randomized to receive prednisone (n = 39) or placebo (n = 20)	Dose: 0.5 mg/kg per day
	Profile: severe asthma	Duration: 2 weeks

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[1] Correspondence to: Emilio Pizzichini. Hospital Universitário da Universidade Federal de Santa Catarina, Núcleo de Pesquisa em Asma e Inflamação das Vias Aéreas (NUPAIVA), Campus Universitário, Trindade, CEP 88040-340, Florianópolis, SC, Brasil. Tel/Fax: 55 48 3234-7711. E-mail: pizzichi@matrix.com.br