One hundred years of immunotherapy: review of the first landmark studies.

In 2011, one hundred years of allergen immunotherapy was celebrated. Several landmark studies date from the first decades of experience with this treatment and are still cited today, often without analysis of the original articles. Original articles of the oldest landmark studies on subcutaneous immunotherapy (SCIT) and sublingual immunotherapy were sought and reviewed in detail, together with some publications on their authors' historical background. Details that might be of importance to the present allergists are highlighted in this article. Study design, preparation of allergen extracts used for immunotherapy and clinical findings of the following studies are discussed. For the European school, Noon 1911 was the first report of successful application of grass pollen extract; Frankland 1954 was the first double-blind placebo-controlled randomized trial (DBPC-RCT) in SCIT. For the European school: Noon published the first report of successful application of grass pollen extract (1911); Frankland was the first double-blind placebo-controlled randomized trial (DBPC-RCT) in SCIT (1954). For the American line: Clowes published the first successful trial of ragweed SCIT (1913); Cooke used skin prick testing as diagnostic method (1915); Loveless used venom immunotherapy with purified venom (not whole body extract) (1956); in 1961/1968 Johnstone showed in a DBPC-RCT dose-effect of an allergen mix and highly significant asthma reduction after up to 14 yrs of treatment of asthmatic children; Lowell and Franklin did the first DB-RCT demonstrating ragweed pollen efficacy as part of a multi-allergen mix and 1967 ragweed pollen extract dose response. We discuss the first studies for SLIT in 1927 from Black (oral-IT versus SCIT) and 1986 from Scadding, DBPC-RCT with house dust mite extract. We conclude that an in-depth review of investigators' observations, methods, and thoughts, however, can also be enriching for investigators in the field today.