Table 3.

Important long-term studies of the link between bronchiolitis and reactive airway disease

			No. patients/controls		Viral etiology (%)			End points and results: patients versus controls (odds ratio, 95% CI P value)
First authora	Year	Design		Age on entry (mo)	RSV	Other	Follow-up time (y)	Recurrent wheezing	Physician-diagnosed asthma	Abnormal pulmonary function test	Atopyb
Sims [74]	1978	Ret	35/35	<12	100c		8	51% vs 3% (P < .001)d		PEF 237 L/mm vs 265 L/min (P < .02)	NS
Pullan [75]	1982	Ret	130/111	<12 (mean 4)	100c		10	42% vs 19% (P < .001)d	NS	Exercise test or histamine challenge positive 25% vs 7% (P < .001)	NS
Mok [76]	1982	Ret	200/200	<12 (mean 4)	50c		7	47% vs 17% (P < .01)d; 11% vs 1% (P < .01)e	9% vs 2.5% (P < .05)d	FEV1 91% vs 95% predicted (P < .005), >10% fall after exercise 53% vs 37% (P < .05)
McConnochie [77]	1984	Ret	59/177	<24			8	44% vs 14% (P < 0.001)e	25% vs 7% (P < 0.001)d, 19% vs 4% (P < 0.001)e
McConnochie [78]	1985	Ret	25/25	<24			8–12			FEF25–75 baseline 64% vs 75% predicted (P = .04), after cold air −9.0% vs −15.7% (P = .04)
McConnochie [79]	1989	Ret	51/102	<24			13	NS	NS
Carlsen [80]	1987	Pro	51/24	<1	61	6f	2	No. episodes, median 3 vs 0 (P < .01)			NS
Osundwa [81]	1993	Ret	70/70	Mean 4 (range 3–8)	100c		2	44% vs 12.9% (P = .001)d
Noble [82]	1997	Pro	61/47	Mean 4 (range 1–12)	66		9–10	34% vs 13% (3.6, 1.3–9.8, P = .018)d	39% vs 13% (4.4, 1.6–12, P = .004)e	Baseline PEF 93% vs 102% predicted (95% CI of differences 4.1–13.4, P < .001), FEV1 91% vs 96% predicted (0.5–9.6, P = .03)	NS
Stein [7]	1999	Pro	68/669	<36	44	28g	6	Year 11: RSV 2.4, 1.3–4.6, P ≤ .01d; Year 13: other virus 3.1, 1.3–7.6, P ≤ .01d; negative test 2.1, 1–4.3, P ≤ .05d		Year 11: RSV FEV1 baseline 2.1, 2.1–2.2, P ≤.001; negative test 2.1, 2.1–2.2, P ≤.05	NS
			56/545				8
			79/634				11
			49/469				13
Weber [83]	1999	Pro	105/105	Median 4 (quartiles 2–6)			3	10% vs 1%e (IRR 7.4, 5.1–17.5)d
Kneyber [84]	2000	Meta-analysish	117/163	<12	0–100		<5	<5 y: 36% vs 6% (5.5, 2.4–12.6)d; ≥5 y: 6% vs 3% (2.4, 0.7–8.4)d			NS
			230/321	<12			≥5
Kotaniemi-Syrjänen [9]	2003	Pro	44	1–24	23c	45ci	6		4.1, 1–16.8 (P = .047)j		NS
Sigurs [8], [48]	2000	Pro	47/93	<12 (mean 4)	100c		7	Year 7: 68% vs 34% (P < .001)d Year 13: NS	Year 13: 37% vs 5.4% (P < .001)d, 28% vs 3.3% (P < .001)e	Year 13: baseline FEV1/FVC 85% vs 88% predicted (P = .001), after β2-agonist 88% vs 89% predicted (P = .043), fall in FEV1 after dry air hyperventilation 6.1% vs 4.6% (P = .047), reversibility NS	Year 7: 41% vs 22% (P = .039) Year 13: NSk
	2004						13
Piippo-Savolainen [85]	2004	Pro	54/45	Median 10 (range 1–24)			19		30% vs 11% (3.4, 1.1–10.1)el	Abnormal pulmonary function 36% vs 11% (4.5, 1.5–13.2)l	NSk

Abbreviations: FEF_25–75, forced expiratory flow at 25–75% range; FEV₁, forced expiratory flow in 1 second; IRR, incidence rate ratio; NS, nonsignificant; PEF, peak expiratory flow; Pro, prospective; Ret, retrospective; RSV, respiratory syncytial virus.

^aOnly the last positive reports are included of studies with many interim analyses.

^bConfirmed by specific IgE antibodies or skin prick test.

^cInclusion criteria.

^dCumulative.

^eCurrently or previous year.

^fParainfluenza n = 2 (4%), rhinovirus n = 1 (2%).

^gParainfluenza n = 68 (14%), other viruses n = 68 (14%) (including adenovirus, influenza virus, cytomegalovirus, rhinovirus, bacterial and mixed infections), negative test n = 129 (27%).

^hIncluding [75], [76], [79], [86].

ⁱRhinovirus n = 20 and virus negative n = 14.

^jBetween rhinovirus-positive and rhinovirus-negative cases.

^kFor any test positive.

^lComparison included pneumonia group, which is not shown.