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Asthma ... in the beginning


An allergic kid taking medicine thru inhaler

… as in so many other afflictions where the cause is not understood, parents seeking help for their children’s asthma problems found themselves blamed for it.

A past president of the College of Allergists was actually quoted in the early 1960s as saying “One of the commonest types of juvenile asthma is caused by an overprotective, domineering mother … the best treatment is a ‘parentectomy’ — separating the child from his mother.”  ~ Allergy Quarterly, Vol. 25

We have come a long way since the 1960s

… in understanding asthma, and we have developed new treatments to control it, but we still don’t know why this disease is continuing to increase in numbers and severity, or how to stop it. There are many things that can bring on an asthma attack in a sensitive individual. Cigarette smoke, pet dander, mold, mildew, pollen, perfumes, and other air-borne irritants can be to blame. So can milk or other foods, and even exercise and cold air. Some studies have even shown that excessive salt can cause a “spastic” condition in the smooth muscles resulting in asthma (as well as high blood pressure).

But there is a significant problem with the studies that seek out causes for asthma. They don’t address the important fact that while many of the asthma triggers are ancient – after all, pets, mildew, and pollen have been around for a while – asthma has only increased dramatically over the past few decades. So, while there is no doubt that any or all of the above can bring about an attack in a sensitive person, they could not account for the sudden rise in occurrence and severity of asthma – especially when so many medical advances have been made in its treatment.

That leaves us to examine those triggers that are relatively new – factors that are found primarily in industrialized countries like the United States (where asthma is rampant) and things that were not in our lives until fairly recently, or that were not used in large quantity until recent years. This includes food additives, increased environmental use of fragrances, and increased exposure to synthetic chemicals of all types.

The Studies

The studies listed below are organized by date, with the most recent date first.  Some of the full texts will need a password because they are kept in a locked file to protect their copyright.  For educational purposes, we are allowed to share the password with you if you write to us.

If you are trying to find a particular author, see the Index below which lists all the primary authors alphabetically with their publication dates.

Author Index
  1. Abrishami 1977
  2. Andrews 2004
  3. Arai 1998
  4. Asmus 1999
  5. Asmus 2001
  6. Barnes 1998
  7. Businco 1995
  8. Ceserani 1978
  9. Chudwin 1986
  10. Corder 1995
  11. Dodson 2012
  12. Egger 1983
  13. Fasmer 2010
  14. Genton 1985
  15. Grzelewska-Rzymowska 1981
  16. Healy 2008
  17. Heiner 1984
  18. Hodge 1996
  19. Hodge 1996a
  20. Hong 1989
  21. Ishihara 1979
  22. Kurek 1996
  23. Lester 1995
  24. Lockey 1977
  25. Longo 1987
  26. Mathison 1985
  27. Miller 1982
  28. Nagakura 2000
  29. Nekam 1998
  30. Neuman 1978
  31. Niles 2000
  32. Pacor 1989
  33. Park 1991
  34. Petrus 1996
  35. Petrus 1997
  36. Sakakibara 1995
  37. Schapowal 1995
  38. Settipane 1975
  39. Settipane 1987
  40. Simon 1994
  41. Spector 1979
  42. Stenius 1976
  43. Timberlake 1992
  44. Towns 1984
  45. Vally 2000
  46. Vally 2002
  47. Vally 2009
  48. Van Bever 1989
  49. Warrington 1986
  50. Wuthrich 1981
  51. Yoneyama 2000
  52. Yusoff 2004
  53. Zheng 1999
Dodson 2012: Chemicals in consumer products

Endocrine disruptors and asthma-associated chemicals in consumer products, Dodson RE1, Nishioka M, Standley LJ, Perovich LJ, Brody JG, Rudel RA., Environmental Health Perspectives, 2012 Jul;120(7):935-43.

BACKGROUND:  Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources.

OBJECTIVES:  We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. …

CONCLUSIONS:  Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in product composition. Consumers should be able to avoid some target chemicals-synthetic fragrances, BPA, and regulated active ingredients-using purchasing criteria. More complete product labeling would enable consumers to avoid the rest of the target chemicals.

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Fasmer 2010: Asthma & ADHD together

Comorbidity of Asthma With ADHD. Fasmer OB, Riise T, Eagan TM, Lund A, Dilsaver SC, Hundal O, Oedegaard KJ,  Journal of Attention Disorders. 2010 Jun 23.

“Objective: To assess how frequently drugs used to treat asthma and ADHD are prescribed to the same patients. … There was a 65% increased overall risk (OR = 1.65) of being prescribed one of the drugs given a prescription of the other. Women had a markedly higher risk than men. When data for each age group (10 years interval) and each gender were analyzed separately, the strongest associations were found for women between 20 and 49 years of age and men between 30 and 49 years of age. Conclusion: These prescription patterns suggested a marked comorbidity between asthma and ADHD.”
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Vally 2009: Diet helps sulfite sensitivity; doctors should be aware of sources.

Clinical effects of sulphite additives. Vally H, Misso NL, Madan V., Clinical and Experimental Allergy. 2009 Nov;39(11):1643-51. Epub 2009 Sep 22.

” Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Topical, oral or parenteral exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however, exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. . . To date, the mechanisms underlying sulphite sensitivity remain unclear, although a number of potential mechanisms have been proposed. Physicians should be aware of the range of clinical manifestations of sulphite sensitivity, as well as the potential sources of exposure. Minor modifications to diet or behaviour lead to excellent clinical outcomes for sulphite-sensitive individuals.
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Healy 2008: Case control study on salicylate-sensitive asthma & fish oil

Control of salicylate intolerance with fish oils. Healy E, Newell L, Howarth P, Friedmann PS., British Journal of Dermatology 2008 Dec;159(6):1368-9. Epub 2008 Sep 15.

“We report three patients with disabling salicylate-induced intolerance who experienced abrogation of symptoms following dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs). All three patients experienced severe urticaria, asthma requiring systemic steroid therapy and anaphylactic reactions. After dietary supplementation with 10 g daily of fish oils rich in omega-3 PUFAs for 6-8 weeks all three experienced complete or virtually complete resolution of symptoms allowing discontinuation of systemic corticosteroid therapy. Symptoms relapsed after dose reduction. Fish oil appears a safe and effective treatment for this difficult and often serious condition.”
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Yusoff 2004: Study on egg-free milk-free diet for asthma

The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study. Yusoff NA, Hampton SM, Dickerson JW, Morgan JB., Journal of the Royal Society of Health 2004 Mar;124(2):74-80

” … The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the ‘experiment’ group, avoiding eggs, milk and their products for eight weeks, or the ‘control’ group, who consumed their customary food. … results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children. ”

Note: Removing eggs and milk also removes most processed foods, commercially baked goods, etc. Is it the avoidance of eggs and milk or the reduction in additives that caused the improvement?

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Andrews 2004: Kind of albuterol & hyperactivity

Impact of racemic albuterol compared to levalbuterol on objective measures of hyperactivity and inattentiveness in children with asthma. W. Andrews, M.H. Teicher, A. Polcari, M. Pankratrz The Journal of Allergy & Clinical Immunology, 113(2), Suppl, S32 (Feb 2004)

“Levalbuterol (LEV) 0.63 mg produces clinically comparable bronchodilation compared with racemic albuterol (RAC) 2.5 mg, but with fewer beta-mediated side effects. Parents complain of increases in hyperactivity and restlessness following treatment with racemic albuterol … Attention and activity were measured using an FDA-approved test (McLean Motion and Attention Test) focused on two of the primary symptoms of ADHD, namely hyperactivity … RAC, but not LEV, resulted in a significant increase in heart rate … In this study, treatment with RAC 2.5 mg significantly increased objective measures of hyperactivity and inattentiveness in asthmatic children compared with LEV 0.63 mg.”

Vally 2002: Aspirin-sensitivity & asthma

The prevalence of aspirin intolerant asthma (AIA) in Australian asthmatic patients. Vally H, Taylor ML, Thompson PJ. Thorax, 2002 Jul;57(7):569-74.

” Aspirin intolerant asthma (AIA) is a clinically distinct syndrome characterised by the precipitation of asthma attacks following the ingestion of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). The prevalence of AIA among Australian asthmatic patients has not previously been reported. … CONCLUSION: The prevalence of respiratory symptoms triggered by aspirin/NSAID use was found to be 10-11% in patients with asthma and 2.5% in non-asthmatics. Aspirin sensitivity appears to be a significant problem in the community and further investigations of the mechanisms of these responses and the possible link between this syndrome and other food and chemical sensitivities are required.”
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Asmus 2001: Double-blind study on additives in asthma treatment

Pulmonary function response to EDTA, an additive in nebulized bronchodilators. Asmus MJ, Barros MD, Liang J, Chesrown SE, Hendeles L.   The Journal of Clinical Allergy and Clinical Immunology. 2001 Jan;107(1):68-72.

” Some nebulized bronchodilator solutions contain additives, such as EDTA, benzalkonium chloride (BAC), or both. OBJECTIVE: Although BAC-induced bronchoconstriction has been well documented in patients with asthma, there is no information on the effects of EDTA on FEV(1) when inhaled in the amounts that would be administered during emergency department treatment of asthma. … CONCLUSION: The amount of EDTA contained in maximum recommended doses of nebulized bronchodilators does not induce bronchospasm. In contrast, BAC induces clinically important bronchospasm, which could decrease the efficacy of a bronchodilator during an emergency.”
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Yoneyama 2000: Effect of DPT & BCG vaccines on asthma & atopy

The effect of DPT and BCG vaccinations on atopic disorders. Yoneyama H, Suzuki M, Fujii K, Odajima Y,  Arerugi, 2000 Jul;49(7):585-92

” …Among the 82 children aged 0-3, out of the 39 who received DPT vaccination, 10 (25.6%) suffered from bronchial asthma and this ratio was significantly higher than among the children who have not received DPT vaccination (1 in 43, 2.3%), … This was also the case concerning atopic dermatitis (… 18.0% vs … 2.3%) . … if … (bronchial asthma, allergic rhinitis and atopic dermatitis) were combined (… 56.4% vs … 9.3%) … From these results, we conclude that DPT vaccination has some effect in the promotion of atopic disorders, …”

Vally 2000: Sulfites & salicylates in wine & asthma

Alcoholic drinks: important triggers for asthma. Vally H, de Klerk N, Thompson PJ, Journal of Allergy and Clinical Immunology, 2000 Mar;105(3):462-7

” … RESULTS: Thirty-three percent of respondents indicated that alcoholic drinks had been associated with the triggering of asthma on at least 2 occasions. Wines were the most frequent triggers, with responses being rapid in onset ( Sensitivity to the sulfite additives in wines seems likely to play an important role in many of these reactions. Sensitivities of individuals to salicylates present in wines may also play a role.”

Niles 2000: Sulfites in cows ... what about in meat?

Sulfur-induced polioencephalomalacia in stocker calves. Niles GA, Morgan SE, Edwards WC, Vet Hum Toxicol 2000 Oct;42(5):290-1

“Calves from 3 farms exhibited blindness, head pressing, and circling before death. Brain lesions confirmed polioencephalomalacia. Excess sulfur was found in the diets on all 3 farms . . . Corn gluten feed and corn steep liquor, . . . corn syrup, corn gluten, corn oil, and corn starch have gained popularity as livestock feeds due to their low prices. With this increased usage as livestock feed, increasing number of cases of polioencephalomalacia have been seen. ”

NOTE: What about the meat of those cows who don’t die? What about people with sulfite sensitivity
(especially asthma) who eat it?

Nagakura 2000: Double-blind study on fish oil, omega-3 for bronchial asthma

Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Nagakura T et al., Eur Respir J 2000 Nov;16(5):861-5

” … The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a randomized controlled fashion. … Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid (EPA) and 36 mg docosahexaenoic acid (DHA) or control capsules containing 300 mg olive oil. . . Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group. In addition, plasma EPA levels increased significantly only in the fish oil group . . .The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma . . .”


Zheng 1999: Vitamin E may suppress nasal allergy

Effect of dietary vitamin E supplementation on murine nasal allergy. Zheng K, Adjei AA, Shinjo M, Shinjo S, Todoriki H, Ariizumi M, American Journal of the Medical Sciences 1999 Jul;318(1):49-54

“Although many studies have reported the effects of dietary vitamin E on the immune response, none so far has assessed its role in nasal allergy. … [this was an animal study] … The results indicate that higher doses of vitamin E supplementation may suppress nasal allergic responses.”

Asmus 1999: Additives in bronchodilators can cause asthma attack

Bronchoconstrictor additives in bronchodilator solutions. Asmus MJ, Sherman J, Hendeles L,  Journal of Allergy and Clinical Immunology, 1999 Aug;104(2 Pt 2):S53-60

” Nebulized bronchodilator solutions are available in the United States as both nonsterile and sterile-filled products. Sulfites, benzalkonium chloride (BAC), or chlorobutanol are added to nonsterile products to prevent bacterial growth… Ethylenediamine tetraacetic acid (EDTA) is added to some products to prevent discoloration of the solution. With the exception of chlorobutanol, all of these additives are capable of inducing bronchospasm in a concentration-dependent manner. However, it is rarely apparent to the patient or health care provider that the additive diminishes the bronchodilator effects. Older products (eg, isoproterenol and isoetharine) contain enough sulfites to produce bronchospasm in most patients with asthma, even in those without a prior history of sulfite sensitivity. Bronchoconstriction from inhaled BAC is cumulative, prolonged, and correlates directly with basal airway responsiveness… If the screwcap product is used in the emergency department, a patient could receive as much as 1800 microg of BAC in the first hour. …Only additive-free sterile solutions should be used for hourly or continuous nebulization of albuterol. …” MedLine || Full Text || Get Password

Nekam 1998: Review on nutritional triggers in asthma

Nutritional triggers in asthma.  Nekam KL, Acta Microbiological et Immunologica Hungarica, 1998;45(1):113-7

” … Exact epidemiological data are lacking, partly because the etiological link is not always obvious, the diagnosis of food hypersensitivity is often complicated and ambiguous, food triggers usually act in concert with other trigger(s),…The participation of airway symptoms in food allergy goes up to 40%… In the therapy avoidance measures are of great importance besides usual asthma therapy, and probably in combination with the reduction of gut permeability.”

Barnes 1998: Possible factors in difficult asthma

Difficult asthma. Barnes PJ, Woolcock AJ, European Respiratory Journal, 1998 Nov;12(5):1209-18

“Asthma is usually easy to manage, but approximately 5% of patients are not controlled even on high doses of inhaled corticosteroids. … There may be unidentified exacerbating factors, including unrecognized allergens, occupational sensitizers, dietary additives, drugs, gastro-oesophageal reflux, upper airway disease, or other systemic diseases, that need to be identified and avoided or treated. …”
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Arai 1998: Study on sulfite & aspirin sensitivity in asthma

Food and food additives hypersensitivity in adult asthmatics. III. Adverse reaction to sulfites in adult asthmatics, Arai Y, Muto H, Sano Y, Ito K, Arerugi  1998 Nov;47(11):1163-7

“…Twenty adult asthmatic patients, who were non-steroid-dependent and without a suggestive history of sulfite sensitivity, underwent challenge with oral solution of metabisulfite. … 12 patients reacted to metabisulfite. They demonstrated airway obstruction 5 (41.7%), urticaria 4 (36.7%), skin manifestation 2 (16.7%) and nasal congestion 1 (8.3%). All patients who demonstrated airway obstruction, were sensitive to aspirin…”

Petrus 1997: Case studies on benzoate intolerance in asthma

Clinico-immunological study of 16 cases of benzoate intolerance in children, Petrus M, Bonaz S, Causse E, Micheau P, Rhabbour M, Netter JC, Bildstein G, Allergie et Immunologie (Paris), 1997 Feb;29(2):36-8

” …Sixteen children (9 boys and 7 girls) were directed to the Hospital of Tarbes from June 1995 to July 1995, for recurring urticaria (7/16) combined with asthma (1/16), atopic eczema (2/16), dermorespiratory syndrome (2/16) and asthma (1/16). All were subject to an immunological examination … whose confirmation is certified by the benefit of the food eviction. … besides food such as grey shrimps, sodas and antibiotic syrups, one finds benzoates in the antiallergic syrups initially prescribed as a preventive measure.”

Petrus 1996: Case study of benzoate allergy in asthma

Asthma and intolerance to benzoates. Petrus M, Bonaz S, Causse E, Rhabbour M, Moulie N, Netter JC, Bildstein G, Archives de Pediatrie, 1996 Oct;3(10):984-7

” …A girl with a family history of asthma … was successfully given continuous bronchodilator therapy until the age of 7 years. At that time, she had more frequent and severe exacerbations … Oral challenges with bisulfite and sodium benzoate… revealed heightened sensitivity to administration of sodium benzoate. Avoidance of this additive was followed by complete and prolonged disappearance of episodes of coughing and wheezing. … Adverse reactions to benzoate in this patient required avoidance of some drugs … prescribed under the form of syrups in asthma. ”
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Kurek 1996: Review of intolerance masquerating as allergy in asthma, hives, etc.

Pseudoallergic reactions. Intolerance to natural and synthetic food constituents masquerading as food allergy. Kurek M, Pediatria Polska, 1996 Sep;71(9):743-52

” Adverse hypersensitivity reactions to natural foods and certain drugs and food additives are mediated by immunological (allergy) or non-immunological mechanisms. …This observation has led to the concept of “pseudoallergic reactions-PAR”. PAR can be triggered in various ways such as: interactions with the central or peripherical nervous system, non-specific release of mediators, enzyme inhibition due to hereditary or pharmacologically induced enzyme deficiencies and pharmacological properties of some natural food constituents such as biogenic amines… PAR to food additives occurs frequently in patients suffering from urticaria, asthma … The same additives (azo dyes, sulphites, benzoates) are used in various drug formulations and may be responsible for eliciting PAR… Skin tests and “in vitro” tests are only sporadically informative. … Individually performed exclusion regimes are the principal methods of prevention.”

Note: The Feingold diet is one way to do this.


Hodge 1996: Fish (omega-3) reduces asthma risk in asthmatic children

Consumption of oily fish and childhood asthma risk. Hodge L, Salome CM, Peat JK, Haby MM, Xuan W, Woolcock AJ. Med J Aust. 1996 Feb 5;164(3):137-40.

” . . . Response rate to the questionnaire was 81.5% (n=468.) After adjusting for confounders such as sex, ethnicity, country of birth, atopy, respiratory infection in the first two years of life and a parental history of asthma or smoking, children who ate fresh, oily fish (>2% fat) had a significantly reduced risk of current asthma (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P<0.01). . . CONCLUSION: These data suggest that consumption of oily fish may protect against asthma in childhood. ”

Quote from full text: “Fish oil contains the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-inflammatory effects”
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Hodge 1996: Chemical intolerance in adult asthma

Assessment of food chemical intolerance in adult asthmatic subjects. Hodge L, Yan KY, Loblay RL., Thorax. 1996 Aug;51(8):805-9.

” . . . A study was undertaken to determine whether changes in bronchial responsiveness to histamine following food chemical challenge without an elimination diet might be a faster, more convenient method. METHODS: Eleven adult asthmatic subjects were challenged twice with metabisulphite, aspirin, monosodium glutamate, artificial food colours, sodium nitrite/ nitrate, 0.5% citric acid solution (placebo), and sucrose (placebo) on separate days. . . . CONCLUSIONS: Strict dietary elimination and measurement of FEV1 after double blind food chemical challenge remains the most reliable method for the detection of food chemical intolerance in asthmatic subjects.”
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Schapowal 1995: Aspirin-sensitive rhinosinusitis, asthma, nasal polyps

Phenomenology, pathogenesis, diagnosis and treatment of aspirin-sensitive rhinosinusitis. Schapowal AG, Simon HU, Schmitz-Schumann M,  Acta Otorhinolaryngologica Belgica, 1995;49(3):235-50

“Aspirin-sensitive rhinosinusitis is a non-allergic, non-infectious perennial eosinophilic rhinitis starting in middle age and rarely seen in children. … There is an intolerance to aspirin and most other NSAID. An intolerance to tartrazine (Yellow 5), food additives, alcohol, narcotics and local anaesthetics can follow. Most aspirin-sensitive patients develop nasal polyps. Untreated, it can lead to asthma. The frequency of aspirin intolerance is 6.18% in patients with perennial rhinitis and 14.68% in patients with nasal polyps. … ”

Sakakibara 1995: Aspirin-induced asthma

Aspirin-induced asthma as an important type of bronchial asthma, Sakakibara H, Suetsugu S, Nihon Kyobu Shikkan Gakkai Zasshi 1995 Dec;33 Suppl:106-15

” Aspirin-induced asthma (AIA) should be recognized as an important types of bronchial asthma … Some patients with AIA are hypersensitive to some agents in addition to NSAID, e.g., tartrazine (15.1%), sodium benzoate (14.3%), and parabens (12.0%). (6) Patients with latent AIA are in danger of having fatal or near-fatal asthma attacks if they take NSAID. We should educate patients to eliminate the risk posed by NSAID and other agents that may induce asthma attacks, and should enlighten doctors and pharmacists, who are not specialists in allergy or respiratory disease, about AIA. (7) Asthma in these patients will be less severe if their condition is correctly diagnosed and they receive appropriate medical treatment.”
MedLine (article in Japanese)

Lester 1995: Review of sulfite sensitivity

Sulfite sensitivity: significance in human health. Lester MR , Journal of the American College of Nutrition, 1995  Jun;14(3):229-32

“… As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s…They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. … Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods… The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. … Broncho-constriction is the most common sensitivity response in asthmatics… Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.”

Corder 1995: Aspirin, salicylate, sulfite, & tartrazine doses for studies on asthma

Aspirin, salicylate, sulfite and tartrazine induced bronchoconstriction. Safe doses and case definition in epidemiological studies. Corder EH, Buckley CE 3rd, Journal of Clinical Epidemiology, 1995 Oct;48(10):1269-75

“Allergic-like reactions to chemical components of foods and medicines may be common. … A 15% decrease in the amount of air expired in one second was defined a positive response. … Doses to which the most sensitive (5%) and practically all (95%) susceptible persons might respectively respond are: metabisulfite 4.6 mg, 255.8 mg; tartrazine 3.4 mg, 885.6 mg; aspirin 0.8 mg, 332.3 mg; and salicylate 2.6 mg, 89.9 mg. Doses within these ranges can be used in epidemiological studies.”
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Businco 1995: Double-blind study on cow's milk and asthma

Food allergy and asthma, Businco L, Falconieri P, Giampietro P, Bellioni B, Pediatric Pulmonology Supplement, 1995;11:59-60

“… The prevalence and incidence of subjects with food-induced wheezing have not been well studied. … Food allergy may trigger allergic respiratory symptoms through two main routes: ingestion or inhalation. …We have shown that a significant proportion of children with IgE-mediated cow’s milk allergy experienced asthma following DBPCOFC [double-blind, placebo-controlled oral food challenge] with cow’s milk.”



Simon 1994: methods of safer oral challenges in asthma

Oral challenges to detect aspirin and sulfite sensitivity in asthma. Simon RA,  Allergie et Immunologie (Paris) 1994 Jun;26(6):216-8

“Oral challenge with aspirin or potential cross-reacting substances … is an effective method for establishing the presence of sensitivity to these substances in asthmatic subjects. Sulfite challenges can be performed in a similar manner. However, many of these subjects have concomitant active irritable airways that could make testing both inaccurate and potentially dangerous. …”

Timberlake 1992: Sodium metabisuphite & asthma in a developing country

Precipitation of asthma attacks in Melanesian adults by sodium metabisulphite. Timberlake CM, Toun AK, Hudson BJ, Papua and New Guinea Medical Journal, 1992 Sep;35(3):186-90

” Seven Melanesian asthmatic patients were challenged with substances that have been shown to precipitate asthma attacks in asthma patients in developed countries. Patients were challenged in a double-blind fashion using placebo and active substances. … All 7 patients were challenged with tartrazine [amount not noted]and sodium metabisulphite; 5 were challenged with aspirin also, but only 2 were challenged with betel nut. Asthma attacks were precipitated by sodium metabisulphite in 3 patients. No other substances precipitated asthma. As sodium metabisulphite is a common food additive, these results suggest that processed foods introduced into developing countries may have an important role in precipitating asthma attacks in susceptible persons.

Park 1991: Case study of aspirin & tartrazine sensitive patient & sodium salicylate

Sodium salicylate sensitivity in an asthmatic patient with aspirin sensitivity, Park HS et al., Journal of Korean Medical Sciences, 1991 Jun;6(2):113-7

” …The result of this study suggests that sodium salicylate may cross-react with aspirin in aspirin-and tartrazine-sensitive patients.”
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Van Bever 1989: Double-blind study on food additives & reactions

Food and food additives in severe atopic dermatitis. Van Bever HP, Docx M, Stevens WJ,  Allergy 1989 Nov;44(8):588-94

“In this study the role of food additives, tyramine and acetylsalicylic acid, was investigated by double-blind placebo-controlled challenges (DBPCC) in 25 children with severe atopic dermatitis (AD). All children challenged with foods (n = 24), except one, showed one or more positive reactions to the DBPCC with foods. Positive reactions presented as different combinations of flares of skin symptoms, intestinal symptoms and respiratory symptoms Six children underwent DBPCC with food additives, tyramine and acetylsalicylic acid. All were found to demonstrate positive skin and/or intestinal reactions to at least one of the food additives. Two children reacted to tartrazine, three to sodium benzoate, two to sodium glutamate, two to sodium metabisulfite, four to acetylsalicylic acid and one to tyramine. It is concluded that some foods, food additives, tyramine and acetylsalicylic acid, can cause positive DBPCC in children with severe AD.
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Pacor 1989: Double-blind study & diet for nasal polyps

Nasal polyps and food intolerance: is there any correlation, Pacor ML et al., Recenti Progressi in Medicina 1989 Jul-Aug;80(7-8):434-7

“In this study the Authors have evaluated the relationship between nasal polyposis and food using elimination diet and the double-blind challenge test. Of twenty-two patients examined, 16 (72.8%) completed the study. Six out of 16 subjects [37%] improved when on diet … Most patients had an alteration of immunological tests involving IgE or circulating immunocomplexes-mediated mechanism.”
MedLine (article in Italian)

Hong 1989: Asthma triggered by aspirin, Yellow 5, benzoates, MSG

Oral provocation tests with aspirin and food additives in asthmatic patients. Hong SP, Park HS, Lee MK, Hong CS, Yonsei Medical Journal, 1989 Dec;30(4):339-45

“Aspirin and food additives are known to induce bronchoconstriction, angioedema or urticaria in susceptible patients. … Significant bronchoconstrictions were found in 15 (41.7%) of the 36 subjects tested. Eight of the 15 subjects showed positive asthmatic responses to the aspirin, two showed asthmatic responses to the food additives, and five responded to both aspirin and the food additives. …”
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Settipane 1987: The Restaurant Syndromes

The Restaurant Syndromes.  Settipane GA. New England Regional & Allergy Proceedings. 1987. 8(1), 39-46.

The Restaurant syndromes can be caused by five major factors: food allergens, sulfites, monosodium glutamate (MSG), tartrazine, and scombroidosis (and other seafood poisoning). A history of atopy and ingestion of known food allergens such as peanuts, egg, fish, and walnuts, together with positive results of skin tests or RAST to these foods, will favor a diagnosis of food allergy. … An extremely rapid onset (minutes) of symptoms consisting of flushing, bronchospasm and hypotension is consistent with a sulfite reaction. Burning, pressure, and tightness or numbness in the face, neck, and upper chest following ingestion of Chinese food favors a diagnosis of adverse reaction to MSG. Also, development of late onset bronchospasm (up to 14 hours) may be related to MSG reactions. Bronchospasm and urticaria in a patient with a history of aspirin intolerance suggests tartrazine sensitivity. … Finally, severe headache or hypertension can result from ingestion of naturally occurring amines, such as tyramine (cheese, red wine) and phenylethylamine (chocolate). …
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Longo 1987: 88% of 82 patients with asthma improved on few-foods diet

Food Allergy in Asthma. Diagnostic Significance of Peripheral Eosinophils, Longo G, Scornavacca G, Strinati R, Poli F,  Pedoatroa Medica e Chirurgica , 1987 Nov-Dec;9(6):663-8

A total of 82 patients with asthma were put on an additive-free “oligoantigenic” diet. Their eosinophil count went down significantly, and improvement of symptoms followed, with significant improvement of lung capacity. Only 10 patients had no improvement.
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Warrington 1986: Food additives & cell-mediated immune response

Cell-mediated immune responses to artificial food additives in chronic urticaria, Warrington RJ, Sauder PJ, McPhillips S,  Clinical Allergy, 1986 Nov;16(6):527-33

“In some cases of chronic urticaria it is suspected that food additives such as tartrazine and sodium benzoate or salicylates may play a role in the pathogenesis of the condition. … It was found that significant production of LIF [T cell-derived lymphokine leucocyte inhibitory factor] occurred in response to tartrazine and sodium benzoate in those individuals with chronic additive induced urticaria. In addition, tartrazine caused LIF release from mononuclear cells of ASA-sensitive asthmatics. These results may indicate a possible role for additive-induced cell-mediated immune responses in the pathogenesis of some cases of chronic urticaria and suggest a potential diagnostic test for this condition.”
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Chudwin 1986: Case study of woman - salicylates caused asthma, urticaria (hives)

Sensitivity to non-acetylated salicylates in a patient with asthma, nasal polyps, and rheumatoid arthritis. Chudwin DS, Strub M, Golden HE, Frey C, Richmond GW, Luskin AT,  Annals of Allergy 1986 Aug;57(2):133-4

” A woman experienced exacerbations of bronchial asthma after taking aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis. On oral challenges, she developed an urticarial reaction after tartrazine; urticarial and bronchospastic reactions after salicylsalicylic acid; and urticarial and bronchospastic reactions after choline magnesium trisalicylate. . . . The results of sensitivity studies of our patient indicates that such patients may also be sensitive to non-acetylated salicylates.

Mathison 1985: Review of aspirin, sulfites & asthma

Precipitating Factors in Asthma: Aspirin, Sulfites, and Other Drugs and Chemicals, Mathison DA, Stevenson DD, Simon RA. Chest. 1985 Jan;87(1 Suppl):50S-54S.

“… Approximately 40 percent of patients with rhinosinusitis, nasal polyps, and asthma and 5 to 10 percent of all asthmatic patients are sensitive to aspirin and aspirin-like nonsteroidal anti-inflammatory drugs … When aspirin/aspirin-like drug is essential for treatment of cardiovascular or musculoskeletal disorder, desensitization by cautious oral challenges with graded doses of aspirin can be accomplished. … Sulfur dioxide and sulfites, commonly used as sanitizers and preservatives of foods and pharmaceuticals, may precipitate acute asthma in 5 percent or more of asthmatic patients. …”
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Note: Also mentioned: drugs such as propranolol (Toprol) can cause bronchospasm, “unmasking” asthma.

Genton 1985: Testing & diet for asthma, urticaria

Value of oral provocation tests to aspirin and food additives in the routine investigation of asthma and chronic urticaria,  Genton C, Frei PC, Pecoud A,  Journal of Allergy and Clinical Immunology, 1985 Jul;76(1):40-5

“…Twenty-four of the 34 patients (nine with asthma and 15 with urticaria) were intolerant to at least one compound. However, no serious reaction was observed. In 20 of these 24 patients [83%](six with asthma and 14 with urticaria), a diet free of additives and nonsteroidal anti-inflammatory drugs resulted, within 5 days, in a marked improvement of symptoms, which persisted 8 to 14 mo after starting the diet…”

Towns 1984: Study on aspirin & sulfite in 29 asthmatic children

Role of acetyl salicylic acid and sodium metabisulfite in chronic childhood asthma. Towns SJ, Mellis CM,  Pediatrics 1984 May;73(5):631-7

“…There was a 66% (19/29) incidence of positive challenge (greater than 20% decrease in forced expiratory volume in one second) with MBS [sodium metabisulfite] and a 21% (6/29) incidence of positive challenge with ASA [aspirin]. . . After 3 months … four of 19 children on the MBS-free diet and one of six on the salicylate-free diet had objective signs of improvement, namely, reduction in asthma medications and/or improvement in lung function. Unfortunately, compliance with the restrictive diet during this 3-month period was poor …”
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Note:  19 of 29 children (65.5%) reacted to sulfite in solution, but none reacted to it given in a capsule. Capsule challenges may not be a good method to show food additive sensitivity.

Heiner 1984: Recurrent earache, rhinitis, large tonsils related to food allergy

Respiratory diseases and food allergy.  Heiner DC, Annals of Allergy 1984 Dec;53(6 Pt 2):657-64

“Both upper and lower respiratory tracts can be affected by food allergy. Manifestations in either may be exclusively due to food allergy (common in infants) or may result from the combined effects of food allergy plus another defect … or a concomitant inhalant allergy. Chronic rhinitis is the most common respiratory tract manifestation of food allergy… Recurrent serous otitis media may be solely or partially due to food allergy. Large tonsillar and adenoid tissues, sometimes with upper airway obstruction, may be caused, or aggravated by, food allergies. Lower respiratory tract disease manifested by chronic coughing, wheezing, pulmonary infiltrates, or alveolar bleeding may also occur. … Food allergy should be considered when there is a history of prior intolerance to a food in childhood or of symptoms beginning soon after a particular food was introduced into the diet. It is an important consideration in patients who have chronic respiratory tract disease which does not respond adequately to the usual therapeutic measures and is otherwise unexplained.”

Egger 1983: Study of diet & migraine (& GI pain, behavior, seizures, asthma, eczema)

Is migraine food allergy? A double-blind controlled trial of oligoantigenic diet treatment,  Egger J et al., Lancet 1983 Oct 15;2(8355):865-9

“93% of 88 children with severe frequent migraine recovered on oligoantigenic diets; … the role of the foods provoking migraine was established by a double-blind controlled trial in 40 of the children. … Associated symptoms which improved in addition to headache included abdominal pain, behaviour disorder, fits, asthma, and eczema. . . .”

Miller 1982: Yellow 5 & asthma, hives, rhinitis

Sensitivity to tartrazine. Miller K., British Medical Journal (Clin Res Ed). 1982 Dec 4;285(6355):1597-8.

“Patients who are sensitive to aspirin may also be sensitive to tartrazine, a yellow dye used in ‘medicines and foods.1 Symptoms of an allergic reaction (urticaria, rhinitis, or asthma) may occur after exposure to many chemicals used to colour, flavour, or preserve food and drugs, but tartrazine (F D & C yellow No 5) is the colour most frequently incriminated.  Intolerance to tartrazine was first reported in 1959, and its part in the induction of intractable urticaria has been recognized since 1975. Non-thrombocytopenic purpura is also reported to be due to hypersensitivity to tartrazine – which suggests the possibility that tartrazine may act as a hapten bound to the endothelial cells of small blood vessels. …People sensitive to acetylsalicylic acid [aspirin] who are allergic to foods should avoid tartrazine as a food dye…”
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Wuthrich 1981: Study on food additive reactions in 620 patients

Acetylsalicylic acid and food additive intolerance in urticaria, bronchial asthma and rhinopathy, Wuthrich B, Fabro L, Schweiz Med Wochenschr 1981 Sep 26;111(39):1445-50

“Adverse reactions (urticaria, angio-edema, bronchoconstriction, purpura) to Aspirin (ASS) and food-and-drug additives such as the yellow dye tartrazine and the preservative benzoate are observed all over the world… it is described as intolerance or pseudo-allergy and has been related to an imbalance of prostaglandin synthesis.  Among 620 patients with urticaria, bronchial asthma or chronic rhinitis, oral provocation tests with ASS, tartrazine or benzoic acid revealed in 165 (26.6%) intolerance to ASS or additives…. More than two thirds of the intolerant patients were improved by an elimination diet and by the avoidance of “aspirin-like” drugs. More than one third of chronic urticaria patients became symptomfree. … Moreover, azo-dyes must no longer be used for colouring of drugs.”
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Grzelewska-Rzymowska 1981: Aspirin intolerance & asthma & nasal polyps

Asthma with aspirin intolerance. Clinical entity or coincidence of nonspecific bronchial hyperreactivity and aspirin intolerance. Grzelewska-Rzymowska I, Rozniecki J, Szmidt M, Kowalski ML, Allergol Immunopathol (Madr) 1981 Nov-Dec;9(6):533-8

“… Nasal and paranasal polyps were found in 77% of the group examined. The sequence of asthma, polyps and aspirin sensitivity has been analyzed. The authors conclude that aspirin – induced bronchoconstriction is the effect of the coincidence of two different phenomena in one subject, i. e. bronchial hyperreactivity and ASA – intolerance.”

Spector 1979: Asthma reactions to salicylate, Yellow 5 & Tylenol

Aspirin and concomitant idiosyncrasies in adult asthmatic patients. Spector SL, Wangaard CH, Farr RS, Journal of Allergy & Clinical Immunology, 1979 Dec;64(6 Pt 1):500-6

” . . . A positive response to oral challenge, defined as a 20% fall in forced expiratory volume in 1 sec  (FEV1) from baseline for up to 4 hr, occurred in 44 of 230 patients with ASA (aspirin), 11 of 277 with tartrazine, 2 of 93 with sodium salicylate, and 2 of 69 with acetaminophen. No one had a positive response to tartrazine, sodium salicylate, or acetaminophen (Tylenol) who was not also positive to ASA. The dose of ASA causing a positive response was less than 5 grains in 95% of the patients. … 96% of those with ASA idiosyncrasy had sinusitis and 71% had nasal polyps. . . ”

Ishihara 1979: Yellow 5 potentiates asthmatic reaction of other bronchoconstrictors

Experimental investigation on the pathogenesis of tartrazine-induced asthma. Ishihara Y, Kitamura S, Tohoku Journal of Experimental Medicine, 1979 Nov;129(3):303-9.

“. . . The contractile responses of guinea pig tracheal tissues induced by various bronchoconstrictors were potentiated in the presence of tartrazine. These results may suggest that tartrazine-induced asthma is not induced by inhibition of PGLS [prostaglandin-like substances] synthesis, but induced by potentiation of bronchoconstrictor responses.”
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Neuman 1978: Yellow 5 & allergy; fibrinolytic pathway

The danger of “yellow dyes” (tartrazine) to allergic subjects, Neuman I, Elian R, Nahum H, Shaked P, Creter D. Clinical Allergy. 1978 Jan;8(1):65-8.

” Oral administration of 50 mg tartrazine to 122 patients with a variety of allergic disorders caused the following reactions: general weakness, heatwaves, palpitations, blurred vision, rhinorrhoea, feeling of suffocation, pruritus and urticaria. There was activation of the fibrinolytic pathway . . .”
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Ceserani 1978: Yellow 5 and asthma

Tartrazine and prostaglandin-system. Ceserani R, Colombo M, Robuschi M, Bianco S., Prostaglandins and Medicine, 1978 Dec;1(6):499-505

” Tartrazine, a dye largely employed for colouring foods, drinks, drugs and cosmetics, induces in some aspirin-sensitive subjects a bronchoconstriction similar to that caused by aspirin and other nonsteroidal anti-inflammatory drugs. . . . Preliminary experiments on aspirin asthmatic patients treated or not with tartrazine are discussed. ”

Lockey 1977: Food dyes make hives & asthma worse

Hypersensitivity to tartrazine (FD&C Yellow No. 5) and other dyes and additives present in foods and pharmaceutical products. Lockey SD Sr,  Annals of Allergy, 1977 Mar;38(3):206-10

“Tartrazine (FD&C Yellow No. 5) and other allowed certified color additives may have an exacerbating effect in chronic urticaria and asthma sufferers. . .”

Abrishami 1977: Review of aspirin intolerance & asthma

Aspirin intolerance–a review. Abrishami MA, Thomas J, Ann Allergy 1977 Jul;39(1):28-37

” Association of bronchial asthma, nasal pathology and intolerance to aspirin is a unique syndrome. Aspirin-induced prolongation of bleeding time, and a tendency for diabetes, may exist with it. … Progression of asthma and nasal polyposis is not prevented by avoidance of aspirin. 4. Salicylates other than aspirin are well tolerated but cross-reactivity with other analgesics, and with tartrazine, may occur. …”

Stenius 1976: Double-blind study of salicylate & Yellow 5 in asthma

Hypersensitivity to acetylsalicylic acid (ASA) and tartrazine in patients with asthma. Stenius BS, Lemola M., Clinical Allergy. 1976 Mar;6(2):119-29.

” One-hundred and forty asthmatics were tested perorally with acetylsalicylic acid (ASA), and/or with the azo-colour tartrazine; a fall in PEF of more than 20% was accepted as a positive result.  About one quarter of the patients displayed a positive reaction to one of the two tested agents. … The frequency of cross-reactivity between the two tested agents was statistically significant; patients reacting to tartrazine were for the most part, also sensitive to ASA. Tests for sensitivity to analgesics and food additives should be conducted as a routine measure in asthmatics, and sensitive patients should be given information on suitable medication and dietary control.”
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Settipane 1975: Aspirin intolerance & asthma, hives

Aspirin intolerance. III. Subtypes, familial occurence, and cross-reactivity with tartarazine. Settipane GA, Pudupakkam RK, J Allergy Clin Immunol 1975 Sep;56(3):215-21

“Evidence has been presented supporting the hypothesis that at least 2 different types of mechanisms may be involved in aspirin intolerance, one resulting in bronchospasm [asthmatic-type difficulty breathing] and the other producing urticaria/angioedema [hives]. Bronchospasm is the predominant symptom of aspirin intolerance in patients who have asthma. In contrast, the predominant symptom of aspirin intolerance in patients who have rhinitis is urticaria/angioedema. . .”

The Diet Connection
The following dyes used in medicines, foods and cosmetics were recognized by the American Academy of Pediatrics Committee on Drugs as being bronchoconstrictors as long ago as 1985:

 Red 2
 Red 3
 Red 4
 Yellow 5
 Yellow 6
 Blue 1
 Blue 2
 Pediatrics. 1985 Oct;76(4):635-43.

What is not often recognized is that a bronchoconstrictor does not have to trigger an asthma attack itself; it can sensitize the airway, preparing it to over-react to the next allergen that comes along. What is bizarre is that even today some medications for asthma actually contain these colorings and other chemicals known to cause broncoconstriction.

Asthma can also be triggered by sulfiting agents used in foods as a preservative. MSG (monosodium glutamate) has also been implicated as a potential asthma trigger for some people. These additives are not eliminated on the Feingold Program, but they are noted on our Foodlists next to products that contain them.

It has long been recognized that aspirin can trigger an attack in some people; what is less well recognized is that those same people may also be sensitive to the aspirin-like salicylate chemicals present in many otherwise-healthy foods such as apples.

What eventually became the Feingold Diet was originally used for asthma and allergies by allergists at the Mayo Clinic and Kaiser Permanente. The Feingold Program is an excellent way to help identify triggers involved in asthma attacks.

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