Table 2.

Summary of influential pediatric long-acting beta agonist ( LABA) and inhaled corticosteroid (ICS) safety studies.

Study	Study design	Drug class	Pediatric only	Time period	Sample size if applicable	Major findings
Allen et al. [1998]	Randomized, blinded, parallel group, placebo-controlled clinical trial	ICS	Yes	1 year	325	ICS-treated children grew at rates similar to placebo-treated control subjects
Bensch et al. [2002]	Randomized, blinded, placebo-controlled clinical trial	LABA	Yes	1 year	518	Incidence of hospitalizations for asthma higher in formoterol groups versus placebo group
Bisgaard [2003]	Meta-analysis covering 8 randomized, blinded, clinical trials for pediatric patients	LABA	Yes	≥6 weeks	2,401	LABA use did not protect pediatric patients from asthma exacerbations compared to patients receiving an ICS, short-acting inhaled β2 agonist (SABA), or placebo; there was a significant increase in asthma-related hospitalizations for children taking a LABA
Castle et al. [1993]	Randomized, blinded, parallel group, clinical trial	LABA	No	16 weeks	25,180	Twelve asthma-related and respiratory deaths in salmeterol group versus two in salbutamol group
Childhood Asthma Management Program Research Group [2000]	Randomized, blinded, placebo-controlled, clinical trial	ICS	Yes	4–6 years	1,041	Children assigned to ICS had lower growth than those assigned to nedocromil (mast stabilizer) or placebo
Garcia Garcia et al. [2005]	Randomized, blinded, noninferiority, clinical trial	ICS	Yes	1 year	994	Children assigned to ICS had lower growth compared with those assigned an leukotriene receptor antagonist
Guilbert et al. [2006]	Randomized, blinded, placebo-controlled, clinical trial	ICS	Yes	2–3 years	285	Children assigned to ICS had lower growth than those assigned to placebo
Guo et al. [2011]	Retrospective population-based cohort study for Medicaid patients ≤40 years old	LABA	No	6 years	940,449	Relative to SABA-only use, LABA use is associated with a higher risk of hospitalization but lower risk of emergency-department visit
Malone et al. [2005]	Randomized, blinded, parallel group, active controlled, clinical trial	LABA/ICS	Yes	12 weeks	203	Safety profile for LABA/ICS treatment similar to that of ICS-only treatment
Nayak et al. [2002]	Randomized, blinded, parallel group, placebo-controlled, clinical trial	ICS	Yes	12 weeks	353	No difference in the incidence or nature of adverse events between ICS and placebo groups
Nelson et al. [2006]	Randomized, blinded, parallel group, placebo-controlled, observational study	LABA	No	28 weeks	26,355	Rate of asthma-related deaths or life-threatening experiences was significantly higher for patients on LABA therapy compared with placebo
Pauwels et al. [2003]	Randomized, blinded, placebo-controlled clinical trial	ICS	No	3 years	7,241	3-year growth in children was reduced in the budesonide group by 1.34 cm; reduction was greatest in the first year
Rodrigo et al. [2009]	Meta-analysis covering 92 randomized, blinded, clinical trials	LABA/ICS	No	≥4 weeks	74,092	LABA/ICS-versus-ICS studies showed that combination therapy reduced exacerbations and hospitalizations and was equivalent to ICS monotherapy in terms of life-threatening events and asthma-related deaths
Simons [1997]	Randomized, blinded, parallel group, placebo-controlled clinical trial	ICS	Yes	1 year	241	Growth was lower in children taking an ICS versus those on a LABA medication or placebo
Tal et al. [2002]	Randomized, blinded, parallel group, double-dummy clinical trial	LABA/ICS	Yes	12 weeks	286	Treatment groups were similar in terms of their adverse-event profile and rates of discontinuation
von Berg et al. [1998]	Randomized, blinded, parallel group, placebo-controlled clinical trial	LABA	Yes	1 year	426	Exacerbation rates did not vary between salmeterol and placebo groups
Zimmerman et al. [2004]	Randomized, blinded, parallel group, placebo-controlled clinical trial	LABA/ICS	Yes	12 weeks	302	No difference in asthma exacerbations between LABA/ICS and ICS-only groups