LAUSR

In 1911, Leonard Noon published a paper in the Lancet entitled ‘Prophylactic inoculation against hay fever’ [1]. Hay fever had first been described in 1819 by John Bostock [2] and had been shown to be caused by grass pollen by Dr James Blackley [3]. Noon believed that the symptoms were caused by a soluble toxin in the grass pollen to which only some persons were sensitive. He believed that inoculations of timothy pollen extract would relieve patients by inducing antitoxins and proceeded with this treatment, the efficacy of which was subsequently reported by John Freeman, also in the Lancet in 1911 [4]. Grass pollen was the major cause of allergic rhinitis (as we now properly call hay fever) in England. In the Eastern United States, similar symptoms occurred later in the summer and were termed autumnal catarrh. This condition had been shown by Wyman to be caused by ragweed pollen [5]. The practice of immunotherapy was rapidly adopted in the United States and applied to ragweed and a number of other pollens as reported by Robert Cooke of New York in 1915 [6]. By 1917, I Chandler Walker of the Peter Bent Brigham Hospital in Boston reported using immunotherapy to treat asthma, employing extracts of cat, dog, and horse dander for treatment [7]. A major addition to the allergens employed for immunotherapy was the introduction of house dust. In 1917, Robert Cooke observed a patient whose asthma remitted on going to Texas for army training and relapsed on returning to New York. He prepared an extract of the patient’s house dust and found not only that the patient reacted to the extract on skin testing, but so also did about 30% of the asthmatic patients in his clinic [8]. Over succeeding decades, it was recognized that house dust from all over the world contained a common allergen to which many allergic patients reacted, but the nature of the allergen remained elusive until the 1960s, when workers in the Netherlands discovered the mite, Dermatophagoides pteronyssinus, in house dust and demonstrated that extracts of the mite produced positive skin tests that paralleled those produced by house dust extracts from around the world [9]. Noon originally prepared his material by extracting timothy pollen in distilled water and then boiling it for 10 min. More standardized and gentler extraction methods were developed by Arthur Fernandez Coca, including a sodium bisulfate-buffered saline solution with phenol as a preservative still known as Coca’s solution [10]. Subsequently, the use of glycerin was introduced to prolong potency of the extracts, although at the expense of painful injections when the concentration was too high [11]. Aluminum precipitation was introduced producing a depoteffect and reducing systemic reactions. Although widely employed in Europe, alum-precipitation has had limited use in the US [12]. To further reduce systemic reactions, extracts were converted to allergoids by the addition of formaldehyde or glutaraldehyde [13]. These preparations would require approval by the US FDA for use in the United States. So, although increasingly employed in Europe, they are not available in this country. In the 1980s and 1990s, the FDA undertook to standardize a number of allergen extracts [14]. Cat pelt and cat hair and dander were standardized to contain a certain amount of the major allergen Fel d 1. Short ragweed was also standardized by the content of its major allergen, Amb a 1. For a group of northern pasture grasses, Bermuda grass, and the house dust mites D. pteronyssinus and D. farinae, on the other hand, potency of the FDA standard preparation was determined by titrated intradermal skin testing. There has been no further progress with standardization in the US in the last two decades. Noon, and those who immediately followed him, administered injections on a preseasonal schedule. Perennial injections for pollen allergy were introduced in the 1920s. The advantages of perennial immunotherapy were that it could be started at any time of year, there was less urgency in reaching maintenance doses, it was more convenient for the patient and the physician, and, furthermore, it appeared to more often be effective since higher doses were achieved. In 1937, Spain and Fuchs reported on their experience with preseasonal and perennial regimens over the previous 5 years [15]. They reported that 73% of the 692 patients treated preseasonally had good results compared to 95% of the 258 treated perennially. Further alternative treatment schedules were introduced by John Freeman who described cluster and rush protocols in 1930 [16]. He reported rushing subjects, in hospital, with extracts of grass pollen, autogenous house dust, codfish, and horse dandruff extracts. He also described the occurrence of frequent systemic reactions during rush protocols.