Table 2:

Selected studies evaluating the role of immunotherapy in the prevention of atopy and asthma

Reference	Population	Study Design	Intervention	Other Clinically Relevant Outcomes	Asthma-Related Outcome
Johnstone DE and Crump L. (1961)48	200 children sensitized to inhalants, age 0–15, with perennial bronchial asthma	Prospective randomized controlled, double-blinded	Each therapy given for 4 years. Control (n=42): SCIT with buffered saline. Intervention 1 (n=49) SCIT 1/10,000,000 weight by volume to all sensitized inhalants based on SPT. Intervention 2 (n=39): SCIT 1/5,000 dilution of all sensitized antigens Intervention 3 (n=43) highest tolerated dose of SCIT, up to 1/250 dilution.	None of the children in Intervention groups 2 or 3 developed new sensitizations while on immunotherapy	At study completion, 64% of the control group displayed wheezing on exertion, while only 9% of those receiving the highest tolerated dose of immunotherapy displayed wheeze with exertion.
Johnstone DE and Dutton A (1968)42	210 children with perennial AR and bronchial asthma were assessed at age 16 for continued asthma symptoms	Prospective randomized placebo-controlled study	The same interventions as above.	Only 12 of 73 children had asthma develop prior to AR. Presence of AR during childhood significantly lessened the likelihood that a child in this study would outgrow asthma by age 16.	22% of placebo-treated children were symptom free, while 72% of treated children were symptom free. (66% of the 1/5000 group, and 78% of the highest tolerated dose group were symptom free.)
Novembre et al. (2004)15	113 children aged 5–14 years with AR and grass allergy, but no prior signs of asthma	Prospective randomized open controlled study	Intervention (n=54): Treated with grass SLIT for 3 years Control (n=59): Standard pharmacotherapy	Treated children had reduced symptoms and used less medication in the second and third years.	There was a four-fold increased rate of asthma development in the children allergic to grass and not treated with IT.
Jacobsen et al. (2007)9	147 subjects, aged 16–25 years, with grass +/− birch pollen allergy	Prospective open, partially RCT	Intervention (n=64): SCIT with standardized birch +/− grass pollen extracts for 3 years. Control (n=53): Standard medical therapy for allergic rhinoconjunctivitis	AR in SCIT group improved significantly more than pharmacotherapy group	10 years later those treated with SCIT had a statistically significant lower rate of asthma than those in the control grou
Marogna et al. (2010)13	78 adult patients, aged 18–65, all monosensitized to HDM	Prospective open, RCT	Intervention 1 (n=19): SLIT to HDM for 3 years Intervention 2 (n=21): SLIT to HDM for 4 years Intervention 3 (n=17): SLIT to HDM for 5 years Control (n=21): pharmacotherapy alone	In Intervention groups, new sensitizations developed in only 21%. In intervention group 1, benefit persisted for 7 years. Intervention groups 2 and 3 had benefit for 8 years. No change in control group, over 15 years, new sensitizations developed in 100%.
Zolkipli et al. (2015)47	111 infants <1 year old at high risk of atopy, but not yet sensitized	Prospective, double blind, RCT	Intervention (n =57): HDM extract given orally twice daily for 12 months Control (n =54): Placebo administered orally twice daily for 12 months	Sensitization to any common allergen 25.5% in control group and only 16% in the intervention group. No effect on AD, or food allergy.	SLIT had no significant preventative effect on wheeze.
Marogna et al. (2017)12	142 patients (age 8–57) with AR, monosensitized to HDM	Prospective open, non-randomized, controlled	Intervention 1 (n=41): Adjuvanted SLIT (Bacterial wall derived adjuvants, that engage TLRs) Intervention 2 (n=43): Standard SLIT Control (n=40): Pharmacotherapy only	After 5 years of treatment, 58% of the control group developed new sensitizations, while 13.2% in the standard SLIT group did and only 8.1% in the adjuvanted group did. Patients treated with SLIT used less medications.	Patients in the control group had a decline in FEV1 over the 5 years of the study, while those treated with IT had stable FEV1.
Valovirta et al. (2018)16	812 children, aged 512 years with AR caused by grass pollen, but no medical history or signs of asthma	Randomized , double-blind, placebo-controlled trial,	Intervention (n=398): 3 years of treatment with grass SLIT Control (n=414): Placebo tablets	Use of AR pharmacotherapy was significantly less in the intervention group. Total IgE, grass pollen specific IgE and SPT reactivity were reduced in the intervention group.	Treatment with grass SLIT in sensitized individuals reduced the risk of experiencing asthma symptoms or using asthma medications at the end of the trial, which was a total of 5 years. Did not significantly prevent asthma.

Abbreviations-- IT: Immunotherapy, SLIT: Sublingual immunotherapy, SCIT: Subcutaneous immunotherapy, SPT: Skin Prick Test, AR: allergic rhinoconjunctivitis, HDM: House dust mite, FEV1: Forced expiratory volume in one second.