Primary Care Asthma Attack Prediction Models for Adults: A Systematic Review of Reported Methodologies and Outcomes

Figures & data

Table 1 Systematic Review Inclusion and Exclusion Criteria

	Inclusion Criteria	Exclusion Criteria
Study types	Longitudinal study	Cross-sectional studies
Population	Adults with asthma, or an asthma population with a mean age of over 18 and a minimum age of 12.	Population with a mean age of 18 or under, or including patients under the age of 12.
Outcome	Asthma attack more than one week after the index date.	Other asthma event or status, such as uncontrolled asthma or severe asthma, or asthma attack recovery.
Settings	Data collected in a clinical setting, such as in general practice or from an asthma nurse.	Data collected in a non-clinical setting, such as using a home-monitoring device
Model metrics	Reported any of the following model performance measures: a confusion matrix, sensitivity, specificity, PPV, NPC, accuracy, balanced accuracy, F1 measure, AUC and AUPRC	Only reported measures of association, such as odds-ratios.

Abbreviations: PPV, Positive predictive value; NPV, negative predictive value; AUC, Area Under the Receiver-Operator Curve; AUPRC, Area Under the Precision-Recall Curve.

Table 2 Summary of Included Studies

1^st Author/ Year	Country	Outcome	Prediction Horizon	Outcome Incidence
Inselman^Citation19 (2023)	USA	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	6 months	22.6%
Jiao^Citation20 (2022)	Canada	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	1 year	0.3%
Lisspers^Citation21 (2021)	Sweden	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	15 days	0.04%
Noble^Citation22 (2021)	UK	Hospitalization	1 year	1.7%
Tong^Citation23 (2021)	USA	Composite: asthma hospitalization or asthma emergency department visit	1 year	1.7%
Wu^Citation24 (2021)	China	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	1 year	33.5%
Zein^Citation25 (2021)	USA	(A) Asthma hospitalization	Not specified: interquartile range 1 to 4 years^a	1.5%
		(B) Asthma emergency department visit		2.9%
		(C) Dispensing of systemic corticosteroids for asthma		32.8%
Luo^Citation16 (2020) (A)	USA	Composite: asthma hospitalization or asthma emergency department visit	1 year	2.4%
Luo^Citation17 (2020) (B)	USA	Composite: asthma hospitalization or asthma emergency department visit	1 year	3.6%
Martin^Citation26 (2020)	USA	Composite: asthma hospitalization, asthma emergency department or immediate care clinic visit, or dispensing of systemic corticosteroids for asthma	1 year	54.8%
Schleich^Citation27(2020)	Belgium	Composite: asthma hospitalization, or dispensing of systemic corticosteroids for asthma	1 year	Not Reported
Xiang^Citation28 (2020)	USA	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	1 year	7.2%
Loymans^Citation29 (2016)^b	Netherlands	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	1 year	13.1%
Bateman^Citation30 (2015)	International	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	6 months	Not Reported
Eisner^Citation31 (2012)	USA	(A) Patient-reported exacerbations (recorded in primary care),	1 year	Not Reported
		(B) Unscheduled primary care visits,
		(C) Asthma hospitalization,
		(D) Asthma emergency department visit
		(E) Dispensing of systemic corticosteroids for asthma
Sato^Citation32 (2009)	Japan	Composite: 2+ consecutive days of a peak expiratory flow rate of ≤70% of baseline, asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	1 year	20.5%
Osborne^Citation33 (2007)	USA	Composite: asthma hospitalization, or asthma emergency department or immediate care clinic visit	30 months	18.2%
Miller^Citation34 (2006)	USA	Composite: self-reported asthma hospitalization or asthma emergency department visit	6 months	8.5%
Peters^Citation35 (2006)	USA	Composite: asthma hospitalization, or asthma emergency department or other acute care center visit	1 year	10.4%
Yurk^Citation36 (2004)^c	USA	(A) Self-reported asthma hospitalization	1 year	9%
		(B) Self-reported asthma emergency department visit		35%
		(C) Missed work 5 or more days in the past month due to asthma (self-reported)		36%
		(D) 5 or more asthma attacks per week in the past month or having symptoms most of the time between attacks (self-reported).		53%
Schatz^Citation15 (2004) [A]	USA	Composite: asthma hospitalization, or asthma emergency department visit	1 year	4.9%
Schatz^Citation18 (2003) [B]	USA	Asthma hospitalization	1 year	1.2%
Lieu^Citation37 (1999)	USA	Composite: asthma hospitalization, or asthma emergency department visit	1 year	6.9%
Ellman^Citation38 (1997)	New Zealand	Composite: a marked decline in FEV1 (≥1.0L or ≥30% from baseline) or dispensing of systemic corticosteroids for asthma	20 weeks	27.5%
Grana^Citation39 (1997)	USA	Asthma hospitalization	1 year	1.8%

Notes: ^aThe study by Zein et al used the entire patient follow-up as the prediction horizon, which varied between patients. The mean was three years, and the interquartile range was 1 to 4 years. The range was not provided. ^bThis study (Loymans et al) has a correction, published in August 2018, which was used in place of the originally reported results. ^cOutcome incidence was only available as an integer for this study (Yurk et al).

Table 3 Methodology of Included Studies

1^st Author/ Year	Algorithm	Outcome	Validation
Inselman^Citation19 (2023):  - Model A  - Model B  - Model C	A. Logistic regression with elastic net B. Random forest C. GBM	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	Internal Validation: random split-sample
Jiao^Citation20 (2022)	Logistic regression with elastic net	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	Internal Validation: random split-sample
Lisspers^Citation21 (2021)	XGBoost^a	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	Internal Validation: random split-sample
Noble^Citation22 (2021)	Logistic regression	Asthma hospitalization	External Validation: patients from Welsh national database
Tong^Citation23 (2021)	XGBoost^a	Composite: asthma hospitalization or asthma emergency department visit	Internal Validation: temporal split
Wu^Citation24 (2021)	Logistic regression with LASSO	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	Both Internal Validation: cross-validation, and External Validation: patients newly recruited after specific time-point
Zein^Citation25 (2021):  - Model A  - Model B  - Model C  - Model D  - Model E  - Model F  - Model G  - Model H  - Model I	A. Logistic regression B. Random forest C. GBM D. Logistic regression E. Random forest F. GBM G. Logistic regression H. Random forest I. GBM	A. Dispensing of systemic corticosteroids for asthma B. Dispensing of systemic corticosteroids for asthma C. Dispensing of systemic corticosteroids for asthma D. Asthma emergency department visit E. Asthma emergency department visit F. Asthma emergency department visit G. Asthma hospitalization H. Asthma hospitalization I. Asthma hospitalisation	External Validation: patients newly diagnosed after specific time-point
Luo^Citation16 (2020) (A)	XGBoost^a	Composite: asthma hospitalization or asthma emergency department visit	Internal Validation: temporal split
Luo^Citation17 (2020) (B)	XGBoost	Composite: asthma hospitalization or asthma emergency department visit	Internal Validation: temporal split
Martin^Citation26 (2020)	Logistic regression	Composite: asthma hospitalization, asthma emergency department or immediate care clinic visit, or dispensing of systemic corticosteroids for asthma	Internal Validation: random split-sample
Schleich^Citation27 (2020)	Logistic regression	Composite: asthma hospitalization, or dispensing of systemic corticosteroids for asthma	External Validation: patients newly recruited after specific time-point
Xiang^Citation28 (2020)	TSANN^a	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	Internal Validation: random split-sample
Loymans^Citation29 (2016)	Logistic regression	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	External Validation: U-BIOPRED^Citation41
Bateman^Citation30 (2015)	Cox regression	Composite: asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	Internal Validation: random split-sample
Eisner^Citation31 (2012):  - Model A  - Model B  - Model C  - Model D  - Model E	Logistic regression	A. Patient-reported exacerbations (recorded in primary care) B. Unscheduled primary care visits C. Asthma hospitalization D. Asthma emergency department visit E. Dispensing of systemic corticosteroids for asthma	Training data performance only
Sato^Citation32 (2009)	CART	Composite: 2+ consecutive days of a peak expiratory flow rate of ≤70% of baseline, asthma hospitalization, asthma emergency department visit, or dispensing of systemic corticosteroids for asthma	Internal Validation: cross-validation
Osborne^Citation33 (2007)^b:  - Model A  - Model B  - Model C	Poisson regression	Composite: asthma hospitalization, or asthma emergency department or immediate care clinic visit	Internal Validation: random split-sample
Miller^Citation34 (2006)	Logistic regression	Composite: self-reported asthma hospitalization or asthma emergency department visit	Internal Validation: temporal split
Peters^Citation35 (2006)^b:  - Model A  - Model B  - Model C  - Model D	CART	Composite: asthma hospitalization, or asthma emergency department or other acute care center visit	Training data performance only
Yurk^Citation36 (2004)^c	Logistic regression	Composite: self-reported asthma hospitalization, self-reported asthma emergency department visit, or self-reporting missing 5 or more days of work in the past month due to asthma	Training data performance only
Schatz^Citation15 (2004) [A]	Logistic regression	Composite: asthma hospitalization, or asthma emergency department visit	External Validation: patients from Fontana, California
Schatz^Citation18 (2003) [B]:  - Model A  - Model B	Logistic regression	Asthma hospitalization	Internal Validation: bootstrap resampling
Lieu^Citation37 (1999):  - Model A  - Model B	CART	Composite: asthma hospitalization, or asthma emergency department visit	Internal Validation: random split-sample
Ellman^Citation38 (1997)  - Model A  - Model B	Logistic regression	Composite: a marked decline in FEV1 (≥1.0L or ≥30% from baseline) or dispensing of systemic corticosteroids for asthma	Training data performance only
Grana^Citation39 (1997)	Logistic regression	Asthma hospitalization	Internal Validation: temporal split

Notes: ^aIn these studies, multiple algorithms were tested, however only the final selected model(s) are reported. ^bThe studies by both Peters and Osborne had multiple models presented, distinguished by the set of predictive features used in the model. ^cA composite of three of the four outcomes presented in Table 2 was used in the final model for Yurk.

Abbreviations: GBM, gradient boosting machine; CART, classification and regression tree; TSANN, Time-Sensitive Attention Neural Network.

Table 4 Binary Classification Measure Performance of Included Studies

1^st Author/ Year	Sensitivity	Specificity	PPV	Balanced Accuracy	F1 Measure
Inselman^Citation19 (2023):
- Model A	68	64	87	66	76
- Model B	81	45	84	63	82
- Model C	73	58	86	66	79
Jiao^Citation20 (2022)	72	57		65
Lisspers^Citation21 (2021)	7		3		4
Noble^Citation22 (2021)	29	93	6	61	10
Tong^Citation23 (2021)	70	91	11	81	19
Wu^Citation24 (2021)	63		72		67
Zein^Citation25 (2021):
- Model A	60	71		66
- Model B	60	67		64
- Model C	64	67		66
- Model D	67	77		72
- Model E	75	78		77
- Model F	84	76		80
- Model G	76	74		75
- Model H	59	86		73
- Model I	86	73		80
Luo^Citation16 (2020) (A)	54	92	23	73	32
Luo^Citation17 (2020) (B)	52	91	11	72	18
Martin^Citation26 (2020)	48	80	74	64	58
Bateman^Citation30 (2015)			40
Sato^Citation32 (2009)	44	92	58	68	50
Osborne^Citation33 (2007):
- Model A			30
- Model B			48
- Model C			48
Peters^Citation35 (2006):
- Model A	1	99	40	50	2
- Model B	17	94	25	56	20
- Model C	7	99	52	53	12
- Model D	11	99	48	55	18
Yurk^Citation36 (2004)	77	63	82	70	79
Schatz^Citation15 (2004) [A]	21	92	17	57	19
Schatz^Citation18 (2003) [B]:
- Model A	45	87	4	66	7
- Model B	47	89	14	68	22
Lieu^Citation37 (1999):
- Model A	49	84	19	67	27
- Model B	36	92	25	64	30
Ellman^Citation38 (1997)
- Model A	11	94	67	53	19
- Model B	27	72	48	50	35
Grana^Citation39 (1997)	70	71		71

Notes: ^aColour code: green = reported, orange = derived. ^bFor Yurk, the composite outcome model was reported. For Peters, the top one and two terminal nodes by risk were used to create the high-risk prediction group.

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