Systematic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment

Figures & data

Figure 1. Study selection.

* Conference proceedings identified from the MedMeme Online Portal for Clinical Intelligence Database.

Table 1. Summary of key studies reporting the prevalence of asthma uncontrolled by GINA Steps 4 or 5 treatment (severe, uncontrolled asthma [SUA]).

Country	Number of studies (number of patients)	How asthma control was defined	SUA in asthma population	SUA in uncontrolled asthma	SUA in severe asthma	Prevalence in the general population
International (France, Germany, Italy, Spain, UK, US)^12	1 (n = 9,734)	ACT < 20	10.0%	NR	79.0%	NR
US^Citation76,Citation78,Citation79,Citation81,Citation83,Citation85,Citation89	7 (n = 320–12.6 million)	Self-assessment of control in the previous 4 weeks; EPR-3 definition: the presence of either risk or impairment; ACT <20 at baseline and 6 months; ≥2 exacerbations^a; ACT < 20 at baseline and every 6 months to 24 months; ≥2 exacerbations^a and high-dosage therapy; ≥3 exacerbations^a; NAEPP guidelines	1.06% (EPR-3)– 49.2% (ACT)	29.9 (EPR-3)–88.0% (≥ 3 exacerbations)	19.9 (≥2 exacerbations)–49.2% (ACT)	0.03 (≥2 exacerbations)
UK (Scotland)^45	1 (n = 267)	BTS guideline	16.9%	NR	NR	NR
France^Citation24–26	2 (n = 491–15,534)	ACT score (<15 very poorly controlled; 15–20 poorly controlled); ANAES (French adaptation of the GINA guidelines); GINA 2006 classification; patient judgment	3.2% (ACT)–18.4% (GINA)	51.2% (GINA)	26.6 (patient judgment)–87.4% (ANAES)	NR
Germany^23	1 (n = 150)	GINA 2009 classification	30.0%	66.2%	38.1%	NR
Italy^28	1 (n = 2,835)	ACT ≤ 15	NR	34.6%	14.2%	NR
Spain^Citation36,Citation37	2 (n = 1,224–36,649)	ACQ >1.5; clinician judgment; GINA guidelines	1.8% (GINA)–3.9% (clinical judgment)	NR	55.7% (ACQ)	NR
Denmark^176	1 (n = 61,583)	High SABA use (≥600 doses of SABA) and/or at least 1 exacerbation in the 1-year period of observation	3.0%	11.7%	36.4%	NR
The Netherlands^53	1 (n = 32,163)	Hospitalization for asthma or use of more than one short (<30 days) course of oral corticosteroids in 2004	0.7%–0.8%	NR	17%	NR
Brazil^Citation71,Citation72,Citation75	3 (n = 275–183 million)	Patient self-assessment; ACQ ≥ 1.5; GINA 2006 classification	38.9% (GINA)	69.9% (GINA)	8.0 (self-assessment)–74.3% (GINA)
South Korea^17	1 (n = 2,298)	ATS criteria for refractory asthma	4.3%	NR	NR	NR
Israel^70	1 (n = 123)	GINA 2006 classification	NR	NR	43.9%	NR

Abbreviations. ACT, Asthma Control Test; ACQ, Asthma Control Questionnaire; ANAES, L’Agence Nationale d’Accreditation et d’Evaluation en Sante; ATS, American Thoracic Society; BTS, British Thoracic Society; EPR-3, The Expert Panel Report 3; GINA, Global Initiative for Asthma; NAEPP, National Asthma Education and Prevention Program; NR, not reported; SABA, short-acting β₂-agonist.

^a Exacerbations per year.

Figure 2. Mean all-cause and asthma-related costs for patients with persistent severe, uncontrolled; and severe, eosinophilic asthma⁹⁰.

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