Kick Wheat and Asthma Rides Off the Back

Mountain Bicyclist Asthma Case:  A male in his forties, a former NORBA sectionals downhill mountain biking champion,  experienced a 40 year history of asthma upon exposure to grass, yard trimmings, or pets. Childhood allergy patch testing showed allergies to most all allergens.  His typical medical routine prior to and following allergen exposure included use of antihistamines, corticosteroids,  and the use of a nebulizer.  This patient experienced a 10 year history of gastro-esophageal reflux disease (GERD).  Treatment included use of  proton pump inhibitors and histamine H2 receptor antagonists.  The acid had inflammed the opening between his esophagus and stomach, the esophageal stricture.  To allow for the passage of food, his gastroenterologist had balloon dilated his esophagus and recommended dilation every six months.   This athlete frequently experienced gastrointestinal (GI) upsets with diarrhea and vomiting. In 1998, his physician diagnosed him with pneumonia and treated him with antibiotics.  To alleviate the long-term asthma, esophagitis and GERD the patient began a wheat gluten free diet (WGFD).

Thirteen years post  WGFD initiation this cyclist no longer has asthma nor requires asthma therapy.  Anti-histamines are occasionally required upon exposure to wheat, grass or pets. He utilizes Citrus sinesis (orange peel extract containing 98.5% d_limonene, 1000mg) or fresh kumquat for reduction of stomach acid. He sleeps on a wedge pillow elevating his chest and head to protect his esophagus from stomach acid.  Instead of needing esophageal balloon dilation at six month intervals, food flowed smoothly until year ten, when his gastroenterologist repeated the procedure.   Patient has contracted no further cases of pneumonia.  He experiences typical cold/flu illnesses less than once each year.  Antibiotics are rarely required and amoxicillin is effective.  Patient maintains GI bacterial balance with acidophilis and lactobacilli probiotics (more discussion on the Gastrointestinal Post on Wheatfreediseasefree.com).  He continues on a WGFD with no ingestion of wheat gluten.

Asthma Discussion:

In the food industry, cross pollinations are utilized to produce high quality wheat (Kuchel et al. 2006).  Gluten protein forms a proteinaceous matrix and a viscous elastic network. Three loci (Glu-A1, Glu-B1, Glu-D1)  present on the long arm of group 1 wheat chromosomes code for wheat gluten (WG) which determines the functional properties of wheat flour including elasticity and shelf life.  (Mondal et al. 2008)  Genetic engineering can be utilized to manipulate these subunits to produce a hearty wheat gluten with strong elastic properties which help bread rise and make it soft and chewy.

In manufacturing, the elastic and tensile properties of wheat gluten are utilized as a matrix material for plastic injection molding.  The resultant glue-like product is a strong oxygen barrier and produces films which are cytotoxic and  restrictive to cell growth (Cho et al. 2011) (Reddy et al. 2010).

Given this genetic modification of wheat, the gastrointestional (GI) system does not digest WG well.  Decomposition occurs by an enzyme called a tissue transaminase producing a gliadin peptide product.  This peptide has a lectin, a powerful agglutinin, which causes inflammatory complexes to be formed within the body. Gliadin is a potent stimulator of the immune system, stimulating T lymphocytes which activate both B lymphocytes and secrete harmful chemicals known as cytokines.   The B lymphocytes produce the allergy Ig E antibodies which bind gliadin, form gliadin-antibody complexes, and are found crosslinked on collagen sites.   The T lymphocyte activated cytokines destroy collagen and activate phagocytes.  Thus, the effect of wheat gluten is in initiating a comprehensive immune cascade which damages collagen both physically through immune complex formation and chemically through cytokine secretion and phagocytic actions.

As gliadin-antibody complexes travel through the circulatory system they attach to various tissues containing collagen.  Collagen is found in the walls or septum of lung tissue where it supports the oxygen-carbon monoxide exchange sacs called alveoli (Ross & Romrell, 1989).   As immune complexes attach septal collagen and damaging chemicals are secreted, the ability of lung tissue to function properly is impaired.  Breathing difficulties and a decreased oxygen tissue saturation results.

Gliadin specific IgE  antibodies may cause both Baker’s asthma and wheat dependent exercise induced anaphylaxis  (Ueno et al. 2010).  While the most prevalent upper respiratory allergen is recognized as grass and tree pollens,  the cross reactivity of IgE antibodies to wheat flour and grass pollens has been demonstrated (Merget et al. 2011). Given this high cross reactivity and the inhalation of flour dust, there is an increased risk that allergic asthma reactions will occur.   Of 25 subjects with mild asthmas and hay fever, given no previous occupational exposure to flour products, each one of these subjects showed sensitization to flour (Merget et al. 2010).  Beyond occupational exposure, bronchial activity leading to asthma, can be associated with food allergy to wheat (Salvatori et al. 2008)

Sinus mucosa undergoes modification when exposed to wheat gluten antigen (WGA).  Respiratory epithelial cells with low quantities of goblet cells are found to change into epithelium with heavy quantities of acid mucin secreting goblet cells.  These are the front line immune response defenders (Otori et al. 1998)   Sialic and fucose residues are produced to immunologically conceal the mannose sugar and carbohydrate moieties from the  WGA.  The resultant disease etiology is sinusitis and allergic rhinitis.  In a wheat challenge test of 23 bakers with a history of wheat flour induced ocular hypersensitivities, 17 subjects had symptoms of rhinitis within 10-30 minutes of wheat flour exposure. (Wittczak, et al. 2007)

While conjunctivitis and urticaria are more prevalent wheat manifestations, respiratory problems are more disabling.  30% of workers in a flour mill were found to have chronic bronchitis or chronic productive cough.  Chest tightness was an affliction of 22% of the workers, while bronchial asthma developed in 18%.  At the end of a work shift three fifths of the workers had a significant drop in Forced Expiratory Volume(FEV) and Forced Vital Capacity(FVC).  Flour disease etiologies were found to match those of cotton, hemp and flax milling. (Awad el Karim, et al. 1986)

In addition to asthma, our male bicyclist experienced esophageal and GI problems.  Our subject was not tested for Celiac Disease (CD), however, rhinitis and nasal allergies are frequently associated with CD.  Gluten peptide inflammation is shown to induce zonulin release in the GI tract opening tight junctions between intestinal cells.  The activity is inserted in to the lamina propria of the gut.  The immune system responds with CD4+  T helper lymphocytes which are sensitive to gluten and  cause damage in the gut and esophagus. (Lucendo, 2011) The  release of T cell mediated cytokine interferon remodel the gut tissue , flattening the mucosa and causing malabsorption.  This is a cytotoxic attack on the epithelium.  (Nova et al. 2010)  Motility disorders in celiac subjects have been reported to affect the gastric mucosa, small bowel, gallbladder and colon.  GERD can develop in untreated CD which is often associated with esophageal maladies. (Lucendo, 2011)

The cure for this plethora of disease is generally considered to be a  gluten free diet (GFD).  A GFD is associated with the resolution and improvement of intestinal and esophageal symptoms in celiac subjects.  Reflux symptoms are relieved and heartburn, chest or epigastric pain, and regurgitation significantly reduced.   With elimination of gluten, the clinical symptoms are reversed.  (Lucendo, 2011)  With a GFD the CD8+ cytotoxic T lymphocyte counts, TCR antibodies  return to normal and the villi recover.  (Nova et al. 2010)

REFERENCES:

Awad el Karim MA, Gad el Rab MO, Omer AA,  El Haimi YAA, “Respiratory and Allergic Disorders in Workers Exposed to Grain and Flour Dusts”, Archives of Environmental Health, September-October 1986, Vol. 41 No. 5

Cho SW, Gallstedt M, Johansson E, Hedenqvist MS, “Injection –Molded Nanocomposites and Material based on Wheat Gluten”, Int J Biol Macromol 2011 Jan 1;48(1):146-52. Epub 2010 Oct 28

Kuchel H, Langridge P, Mosionek L, Williams K, Jefferies SP, “The Genetic Control of Milling Yield, Dough Rheology and Baking Quality of Wheat”, Theor Appl Genet, 2006 May;112(8);1487-95. Epub 2006 Mar 21

Lucendo AJ,  “Esophageal Manifestations of Celiac Disease”,  Dis Esophagus 2011 Mar 25. Doi: 10.1111/j.1442-2050.2011.01190.x. [Epub ahead of print]

Merget R, Sander I, van Kampen V, Bechmannn U, Heinze E, Raulf-Heimsoth M, Bruening T, “Allergic Asthma after Flour Inhalation in Subjects without Occupational Exposure to Flours: an Experimental Pilot Study”, Int Arch Occup Environ Health; 2011 Jan 30 [Epub ahead of print]

Mondal S, Tilley M, Alviola JN, Waniska RD, Bean SR, Glover KD, Hays DB, “Use of Near-isogenic Wheat Lines to Determine the Glutenin Composition and Functionality Requirements for Flour Tortillas”, J Agric Food Chem 2008 Jan 9;56(1);179-84. Epub 2007 Dec 12.

Nova E, Pozo T, Sanz, Marcos A, 3rd International Immunonutrition Workshop.  Session 4: Dietary Strategies to Prevent and Mitigate Inflammatory Disease.  Dietary Strategies of Immunomodulation in Infants at Risk for Celiac Disease, Proceedings of the Nutrition Society (2010), 69, 347-353

Otori N, Carlsoo B, Stierna P, “Changes in Glycoconjugate Expression of the Sinus Mucosa during Experimental Sinusitis: A Lectin Histochemical Study of the Epithelium and Goblet Cell Development”, Acta Otolaryngol (Stockh) 1998; 118: 248-256

Reddy N, Jiang Q, Yang Y, “Novel Wheat Protein Film as Substrates for Tissue Engineering”,  J Biomater Sci Polym Ed 2010 Occt 27. [Epub ahead of print]

Ross, Michael H., Romrell, Lynn J., “Histology, A Text and Atlas”, Second Edition, 1989

Salvatori N, Reccardini F, Convento M, Purinan A, Colle R, De Carli S, Garzoni M, Lafiandra D, De Carli M, “Asthma Induced by Inhalation of Flour in Adults with Food Allergy to Wheat”, Clin Exp Allergy, 2008 Aug;38(8):1349-56. Epub 2008 May 28

Ueno M, Adachi A, Fukumoto T, Nishitani N, Fujiwara N, Matsuo H, Kohno K, Morita E, “[Analysis of Causative Allergen of the Patient with Baker’s Asthma and Wheat-Dependent Exercise-Induced Anaphylaxis (WDEIA)]”, Arerugi, 2010 May;59(5):552-7.

Wittczak T, Krakowiak A, Walusiak J, Pas-Wyroslak A, Kowalczyk M, Palczynski C, “Challenge Testing in the Diagnosis of Occupational Allergic Conjunctivitis”, Occupational Medicine 2007;57:532-534

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Updated January 20, 2013

Photograph: Traveling on the Pacific Coast Highway 1 south of Hearst Castle.

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