Anti-inflammatory dosing of theophylline in the treatment of status asthmaticus in children

Figures & data

Table 1 Generalized linear mixed-effects models in which the outcomes were made a function of theophylline, smoke exposure, ICS, LABA, and oxygen

Outcome	Predictor	B (95% CI)	P-value
LOS (hours)	Theophylline	−21.17 (−10.1, −32.2)	<0.001**
	Smoke exposure	2.50 (−7.9, 12.7)	0.633
	ICS	9.22 (−21.1, 2.6)	0.125
	LABA	−6.10 (−7.2, 19.0)	0.380
	Oxygen	−14.76 (−0.9, 30.2)	0.063
Time to off O2 (hours)	Theophylline	−15.88 (−0.42, −31.3)	0.044**
	Smoke exposure	0.954 (−13.5, 15.4)	0.896
	ICS	11.71 (−27.8, 4.8)	0.155
	LABA	−12.35 (−6.4, 31.1)	0.194
	Oxygen	–	–
Time to PFT (hours)	Theophylline	−16.6 (−3.4, −29.8)	0.014**
	Smoke exposure	7.55 (−4.8, 19.9)	0.229
	ICS	10.84 (−25.8, 4.2)	0.155
	LABA	−4.74 (−10.8, 0.3)	0.547
	Oxygen	−22.4 (−4.7, − 40.2)	0.014**
Time to q4h albuterol (hours)	Theophylline	−23.2 (−11.6, −34.8)	<0.001**
	Smoke exposure	7.96 (−2.9, 18.8)	0.149
	ICS	7.97 (−20.3, 4.4)	0.205
	LABA	−8.78 (−5.3, 22.9)	0.220
	Oxygen	−21.23 (−5.45, −37.0)	0.009**
Costs (dollars)	Theophylline	−$2746 (−$4K, −$1K)	<0.001**
	Smoke exposure	$856 (−$553, $2K)	0.232
	ICS	$1235 (−$3K, $380)	0.133
	LABA	−$688 (−$1K, $2K)	0.452
	Oxygen	−$4241 (−$2K, −$6K)	<0.001**

Note:

** P<0.05.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LOS, length of stay; PFT, pulmonary function testing; CI, confidence interval; q4h, every 4 hours.

Table 2 Cox regression models in which the timed outcomes were made a function of theophylline, smoke exposure, ICS, LABA, and oxygen

Outcome	Predictor	HR (95% CI)	P-value
LOS (hours)	Theophylline	1.75 (1.20–2.54)	0.004**
	Smoke exposure	0.97 (0.76–1.51)	0.690
	ICS	0.81 (0.55–1.20)	0.294
	LABA	1.16 (0.73–1.82)	0.535
	Oxygen	1.38 (0.81–2.33)	0.237
Time to off O2 (hours)	Theophylline	1.68 (1.12–2.54)	0.012**
	Smoke exposure	0.94 (0.64–1.36)	0.727
	ICS	0.68 (0.45–1.03)	0.068
	LABA	1.59 (0.97–2.63)	0.064
	Oxygen	–	–
Time to PFT (hours)	Theophylline	2.12 (1.34–3.39)	0.001**
	Smoke exposure	0.99 (0.66–1.48)	0.950
	ICS	0.72 (0.45–1.17)	0.187
	LABA	1.40 (0.82–2.38)	0.216
	Oxygen	2.63 (1.40–4.94)	0.003**
Time to q4h albuterol (hours)	Theophylline	2.43 (1.61–3.39)	<0.001**
	Smoke exposure	1.04 (0.72–1.50)	0.847
	ICS	0.74 (0.48–1.12)	0.155
	LABA	1.44 (0.87–2.37)	0.158

Note:

** P<0.05.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LOS, length of stay; PFT, pulmonary function testing; HR, hazards ratio; CI, confidence interval; q4h, every 4 hours.

Figure 1 Summary of treatment algorithm for status asthmaticus at Kosair Children’s Hospital.

Notes: The algorithm was developed by institution’s (Kosair Children’s Hospital) multidisciplinary asthma task force based on 2007 National Asthma Education and Prevention Program (NAEPP) guidelines. Patients on oral steroids were treated with prednisolone at 1 mg/kg/dose BID, while those on IV steroids were treated with methylprednisolone 1 mg/kg/dose every 6 hours.
Abbreviations: ICU, intensive care unit; q2h, every 2 hours; q3h, every 3 hours; q4h, every 4 hours; IV, intravenous; prn, pro re nata; PICU, pediatric ICU; BID, twice a day; FEV₁, forced expiratory volume in 1 second; MD, medical doctor.

Table 3 Patient characteristics and outcomes stratified by receiving theophylline or not receiving theophylline during their stay in the hospital

Categorical variable	Theophylline N=57 (%)	No theophylline N=109 (%)	P-value
Male	32 (56.1)	66 (60.6)	0.583
Ethnicity			0.273
Black	35 (61.4)	68 (62.4)
White	19 (33.3)	39 (35.8)
Other	3 (5.3)	2 (1.8)
PICU	27 (47.4)	58 (53.2)	0.475
Smoking exposure	31 (54.4)	35 (32.1)	0.005**
History of asthma	55 (96.5)	106 (97.3)	0.787
History of atopy	36 (65.5)	51 (58.0)	0.371
IV steroid	27 (47.4)	34 (31.2)	0.040**
LTRA	36 (33.1)	27 (47.4)	0.071
ICS	44 (76.8)	55 (50.5)	0.001**
LABA	20 (35.1)	21 (19.3)	0.025**
Oxygen	53 (93.0)	88 (80.7)	0.036**
Anticholinergics	1 (1.8)	0 (0.0)	0.167
Magnesium	45 (79.0)	95 (87.2)	0.167

Continuous variable	Theophylline Mean (SD)	No theophylline Mean (SD)	P-value
Age (years)	10.1 (3.2)	10.1 (3.4)	0.988
FEV1 (% predicted)	77.6 (15.4)	78.3 (15.0)	0.820
FEF 25–75 (% predicted)	60.0 (20.4)	60.0 (20.7)	0.991
FEV1/FVC ratio	0.79 (0.09)	0.80 (0.09)	0.516
TLC (% predicted)	100.8 (18.0)	96.4 (17.8)	0.359
RV (% predicted)	167.8 (63.2)	159.3 (57.9)	0.596
RV/TLC ratio	0.33 (0.090	0.34 (0.10)	0.955
Time to off O2 (hours)	73.2 (45.1)	56.5 (34.5)	0.014**
Time to PFT (hours)	120.9 (37.2)	106.8 (26.9)	0.023**
Time to albuterol every 4 hours (hours)	123.8 (36.0)	102.6 (29.2)	<0.001**
LOS (hours)	135.6 (35.5)	116.2 (26.2)	<0.001**
Costs (dollars)	$14,325 ($5K)	$12,050 ($4K)	0.002**

Note:

** Significant at the 0.05 level.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LOS, length of stay; PFT, pulmonary function testing; IV, intravenous; PICU, pediatric intensive care unit; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF, forced expiratory flow; RV, residual volume; TLC, total lung capacity; LTRA, leukotriene receptor antagonist; SD, standard deviation.