Risk Factors Associated with Irreversible Airway Obstruction in Asthma: A Systematic Review and Meta-Analysis

Table 1

Included studies.

Author	Year	Study design	Country	Population number	Defining IAO	Follow-up time	Increase risk factor	Decrease risk factor
Martinez et al. [41]	1995	Cohort study	Tucson	826	Persistent wheezing	6 yrs	Maternal asthma; maternal smoking; rhinitis apart from colds; Hispanic ethnic background	Rhinosinusitis
Ulrik and Backer [3]	1999	Cohort study	Denmark	31	FEV1 < 80% predicted and change in FEV1 after 5 mg salbutamol < 9% pred	10 yrs	Long-term treatment with oral corticosteroids	—
Ten Brinke et al. [6]	2001	Cohort study	Netherlands	132	Postbronchodilator FEV1 or FEV1/FVC < 75% predicted, using inhaled corticosteroids (1,600 g/d) and/or daily oral prednisone and long-acting bronchodilators for 1 yr	>1 year	Sputum eosinophils ≥ 2%; PC20; histamine 1.0 mg/mL; adult onset of asthma	—
Vonk et al. [8]	2003	Case control	Netherlands	228	FEV1 < 80% predicted and reversibility < 9% predicted	26 years	—	Use of steroids; ln (slope BHR)
Sears et al. [33]	2003	Cohort study	New Zealand	613	FEV1 of less than 75% of the FVC at 9 and 11 years of age and of less than 70% of the FVC at older ages, but spirometry was repeated 10 minutes after they had inhaled nebulized albuterol (5 mg per milliliter) for 2 minutes	26 years	Sex; PC20; positive skin test and age at onset of wheezing	Father smoked when study; member was a child
Bumbacea et al.; [32]	2004	Case control	UK	66	FEV1 < 50% predicted; these were postbronchodilator FEV1 and had not varied by > 10% when repeated within 3–6 months.	3–6 months	Bronchial thickening and bronchial dilatation; peripheral blood eosinophil	—
Covar et al. [40]	2004	Cohort study	Colorado	990	At least 1% per year loss in postbronchodilator FEV1% predicted. Participants who had a significant reduction in postbronchodilator FEV1% predicted (SRP)	2 yrs	—	Male sex; age
Mascia et al. [11]	2005	Case control; (TENOR)	USA	4756	2 or more oral corticosteroid bursts during the 12 months before enrollment, current use of 3 or more medications or chronic daily high doses of inhaled corticosteroids, or use of 5 mg or more of oral prednisone per day.	3-year, multicenter, observational study	Aspirin sensitivity	—
Limb et al. [35]	2005	Cohort study	USA	121	Postbronchodilator FEV1, forced vital capacity, or FEV1/FVC% less than or equal to the 5th percentile or 2 or more indices less than or equal to the 10th percentile (National Health and Nutrition Examination Survey III normative data)	10 yrs	Prematurity	—
Lee et al. [5]	2007	Case control; (TENOR study)	USA	1017	Postbronchodilator FEV1/FVC ratio < 70% at two annual consecutive visits	2 yrs	Older age; Black patients; male; smoking; aspirin sensitivity	Hispanic ethnicity; college education or advanced degree; family history of atopic dermatitis; dust sensitivity
Jang et al. [36]	2007	Case control	Korea	582	FEV1/FVC and a predicted FEV1 of < 75%	1 yr	Age and asthma duration	BMI
Liebhart et al. [37]	2008	Case control	Poland	110	The predicted value of FEV1% predicted after bronchodilator administration 80%		Male; disease duration; smoking	—
Kaminska et al.; [32]	2009	Case control	Canada	34	Prebronchodilator FEV1 < 70% of predicted value and FEV1/FVC ratio < 80% of predicted value at each visit	At least 12 months	—	—
Contoli et al. [31]	2010	Case control	Italy	31	Postbronchodilator FEV1/FVC < 70%	5 yrs	—	—
Jang et al. [38]	2010	Cohort study	Korea	674	FEV1/FVC and a predicted FEV1 of <75% following bronchodilator	1 yr	Asthmatics without rhinitis	—
Lee et al. [4]	2011	Case control	Korea	235	FEV1/FVC ratio < 70% on all of three pulmonary function tests despite use of high-dose inhaled corticosteroids (ICS) and long-acting b2-agonists (LABA)	3 months	Smoking more than 5 pack-years; asthma more than 15 years	Rhinosinusitis
Perret et al. [39]	2013	Cohort study	USA	8,583	Postbronchodilator FEV1/FVC less than the lower limit of normal, regardless of postbronchodilator reversibility	44 yrs	Smoking; atopy	—
Gupta et al. [30]	2007	Case control	USA	73	Daily high-dose administration of ICS 800 mg budesonide or ≥ 400 mg fluticasone/momethasone per day in combination with LABA and/or LTRA	1 year	—	—

FEV1: forced expiratory volume in 1 second; FEV1/FVC: forced expiratory volume in 1 second/forced vital capacity; BMI: body mass index; yr: year.