Immune-mediated inflammatory diseases

[Jhanananda]

Immune-mediated inflammatory diseases

An immune-mediated inflammatory disease (IMID) is any of a group of conditions or diseases that lack a definitive etiology, but which are characterized by common inflammatory pathways leading to inflammation, and which may result from, or be triggered by, a dysregulation of the normal immune response. All IMIDs can cause end organ damage, and are associated with increased morbidity and/or mortality.

Inflammation is an important and growing area of biomedical research and health care because inflammation mediates and is the primary driver of many medical disorders and autoimmune diseases, including ankylosing spondylitis, psoriasis, psoriatic arthritis, Behcet's disease, arthritis, inflammatory bowel disease (IBD), and allergy, as well as many cardiovascular, neuromuscular, and infectious diseases. Some current research even suggests that aging is a consequence, in part, of inflammatory processes.

Characterization
IMID is characterized by immune disregulation, and one underlying manifestation of this immune disregulation is the inappropriate activation of inflammatory cytokines, such as IL-12, IL-6 or TNF alpha, whose actions lead to pathological consequences.

[Jhanananda]

I stumbled across this condition yesterday, and saw that it might just be the description of my medical condition with the inflammatory agent being seasonal allergies, which has led to various organ deterioration, specifically the pancreas, leading to type II diabetes.

[Jhanananda]

I have come to realize that my decline in health after moving to Prescott, AZ is due to Immune-mediated inflammatory diseases, such as allergies.  I have been seeing an allergist for about 9 months, and I have been taking high doses of antihistamines for nearly a year now, with impressive results in improved health, and weight loss of over 50lbs in 1 year.

A resent test showed that I have a total of 2692 Immunoglobulin E.  At that time I was tested for 25 common allergens.  Among the things that I am allergic to, I am extremely allergic to: cat dander, mountain cedar, American elm, olive tree, cottonwood, Russian thistle, common pigweed, and sheep sorrel.

Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) "isotype") that has only been found in mammals. IgE is synthesised by plasma cells.  IgE's main function is immunity to parasites such as helminths[2] like Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica.[3][4][5] IgE is utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum.[6]

IgE also has an essential role in type I hypersensitivity,[7] which manifests in various allergic diseases, such as allergic asthma, most types of sinusitis, allergic rhinitis, food allergies, and specific types of chronic urticaria and atopic dermatitis. IgE also plays a pivotal role in responses to allergens, such as: anaphylactic drugs, bee stings, and antigen preparations used in desensitization immunotherapy.

Variations in the upper limit of normal total serum IgE have been reported: they can range from 150 to 1,000 UI/ml; but the usually accepted upper limit is between 150 and 300 UI/ml.

So, I have 2.5x the upper end of normal total serum IgE, which has led to: type II diabetes, COPD and coronary heart disease.

Type  I hypersensitivity (or immediate hypersensitivity) is an allergic reaction provoked by reexposure to a specific type of antigen referred to as an allergen.[1] Type I is not to be confused with type II, type III, or type IV hypersensitivities, nor is it to be confused with Type I Diabetes or Type I of any other disease or reaction.

Exposure may be by ingestion, inhalation, injection, or direct contact.

Pathophysiology

In type 1 hypersensitivity, B-cells are stimulated (by CD4+TH2 cells) to produce IgE antibodies specific to an antigen. The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1 hypersensitivity, the antibody is IgE instead of IgA, IgG, or IgM. During sensitisation, the IgE antibodies bind to FcεRI receptors on the surface of tissue mast cells and blood basophils.[2] Mast cells and basophils coated by IgE antibodies are "sensitized". Later exposure to the same allergen cross-links the bound IgE on sensitized cells, resulting in anaphylactic degranulation, which is the immediate and explosive release of pharmacologically active pre-formed mediators from storage granules and concurrent synthesis of inflammatory lipid mediators from arachidonic acid;[3] some of these mediators include histamine, leukotriene (LTC4 and LTD4), and prostaglandin, which act on proteins (e.g., G-protein coupled receptors) located on surrounding tissues.[3] The principal effects of these products are vasodilation and smooth-muscle contraction.

Type 1 hypersensitivity can be further classified into immediate and late-phase reactions. The immediate hypersensitivity reaction occurs minutes after exposure and includes release of vasoactive amines and lipid mediators, whereas the late-phase reaction occurs 2–4 hours after exposure and includes the release of cytokines.[4]

[Alexander]

Good to hear, Jeff, that you found the source of those health problems! Hopefully now the doctor can diagnose a way to address them.

[Jhanananda]

Thanks, Alexander.  That is my hope.

[Jhanananda]

From studying this subject I have come to realize that a number of my symptoms fall into the category of Anaphylaxis.

Anaphylaxis
Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.[4][5] It typically causes more than one of the following: an itchy rash, throat or tongue swelling, shortness of breath, vomiting, lightheadedness, and low blood pressure.[1] These symptoms typically come on over minutes to hours.[1]

Common causes include insect bites and stings, foods, and medications.[1] Other causes include latex exposure and exercise.[1] Additionally cases may occur without an obvious reason.[1] The mechanism involves the release of mediators from certain types of white blood cells triggered by either immunologic or non-immunologic mechanisms.[6] Diagnosis is based on the presenting symptoms and signs after exposure to a potential allergen.[1]

The primary treatment of anaphylaxis is epinephrine injection into a muscle, intravenous fluids, and positioning the person flat.[1][7]

Worldwide, 0.05–2% of the population is estimated to experience anaphylaxis at some point in life.[3] Rates appear to be increasing.[3] It occurs most often in young people and females.[7][8] Of people who go to a hospital with anaphylaxis in the United States about 0.3% die.[9]

Signs and symptoms
Anaphylaxis typically presents many different symptoms over minutes or hours[7][11] with an average onset of 5 to 30 minutes if exposure is intravenous and 2 hours if from eating food.[12] The most common areas affected include: skin (80–90%), respiratory (70%), gastrointestinal (30–45%), heart and vasculature (10–45%), and central nervous system (10–15%)[13] with usually two or more being involved.[3]

Symptoms typically include generalized hives, itchiness, flushing, or swelling (angioedema) of the afflicted tissues.[4] Those with angioedema may describe a burning sensation of the skin rather than itchiness.[12] Swelling of the tongue or throat occurs in up to about 20% of cases.[14] Other features may include a runny nose and swelling of the conjunctiva.[15] The skin may also be blue tinged because of lack of oxygen.[15]
Respiratory

Respiratory symptoms and signs that may be present include shortness of breath, wheezes, or stridor.[4] The wheezing is typically caused by spasms of the bronchial muscles[16] while stridor is related to upper airway obstruction secondary to swelling.[15] Hoarseness, pain with swallowing, or a cough may also occur.[12]

Cardiovascular

Coronary artery spasm may occur with subsequent myocardial infarction, dysrhythmia, or cardiac arrest.[3][13] Those with underlying coronary disease are at greater risk of cardiac effects from anaphylaxis.[16] The coronary spasm is related to the presence of histamine-releasing cells in the heart.[16] While a fast heart rate caused by low blood pressure is more common,[15] a Bezold–Jarisch reflex has been described in 10% of cases where a slow heart rate is associated with low blood pressure.[8] A drop in blood pressure or shock (either distributive or cardiogenic) may cause the feeling of lightheadedness or loss of consciousness.[16] Rarely very low blood pressure may be the only sign of anaphylaxis.[14]
Other

Gastrointestinal symptoms may include crampy abdominal pain, diarrhea, and vomiting.[4] There may be confusion, a loss of bladder control or pelvic pain similar to that of uterine cramps.[4][15] Dilation of blood vessels around the brain may cause headaches.[12] A feeling of anxiety or of "impending doom" has also been described.[3]

Causes

Anaphylaxis can occur in response to almost any foreign substance.[17] Common triggers include venom from insect bites or stings, foods, and medication.[8][18] Foods are the most common trigger in children and young adults while medications and insect bites and stings are more common in older adults.[3] Less common causes include: physical factors, biological agents such as semen, latex, hormonal changes, food additives such as monosodium glutamate and food colors, and topical medications.[15] Physical factors such as exercise (known as exercise-induced anaphylaxis) or temperature (either hot or cold) may also act as triggers through their direct effects on mast cells.[3][19] Events caused by exercise are frequently associated with the ingestion of certain foods.[12] During anesthesia, neuromuscular blocking agents, antibiotics, and latex are the most common causes.[20] The cause remains unknown in 32–50% of cases, referred to as "idiopathic anaphylaxis."[21] Six vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal) are recognized as a cause for anaphylaxis, and HPV may cause anaphylaxis as well.[22] Physical exercise is an uncommon cause of anaphylaxis;[23] in about a third of such cases there is a co-factor like taking an NSAID or eating a specific food prior to exercising.[24]

Food

Many foods can trigger anaphylaxis; this may occur upon the first known ingestion.[8] Common triggering foods vary around the world. In Western cultures, ingestion of or exposure to peanuts, wheat, nuts, certain types of seafood like shellfish, milk, and eggs are the most prevalent causes.[3][13] Sesame is common in the Middle East, while rice and chickpeas are frequently encountered as sources of anaphylaxis in Asia.[3] Severe cases are usually caused by ingesting the allergen,[8] but some people experience a severe reaction upon contact. Children can outgrow their allergies. By age 16, 80% of children with anaphylaxis to milk or eggs and 20% who experience isolated anaphylaxis to peanuts can tolerate these foods.[17]

Medication

Any medication may potentially trigger anaphylaxis. The most common are β-lactam antibiotics (such as penicillin) followed by aspirin and NSAIDs.[13][25] Other antibiotics are implicated less frequently, and the reactions to NSAIDs are agent specific meaning that those who are allergic to one NSAID can typically tolerate a different one.[25] Other relatively common causes include chemotherapy, vaccines, protamine and herbal preparations.[3] Some medications (vancomycin, morphine, x-ray contrast among others) cause anaphylaxis by directly triggering mast cell degranulation.[8]

The frequency of a reaction to an agent partly depends on the frequency of its use and partly on its intrinsic properties.[26] Anaphylaxis to penicillin or cephalosporins occurs only after it binds to proteins inside the body with some agents binding more easily than others.[12] Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in fewer than one in every 50,000 courses of treatment.[12] Anaphylaxis to aspirin and NSAIDs occurs in about one in every 50,000 persons.[12] If someone has a reaction to penicillins, his or her risk of a reaction to cephalosporins is greater but still less than one in 1,000.[12] The old radiocontrast agents caused reactions in 1% of cases, while the newer lower osmolar agents cause reactions in 0.04% of cases.[26]

Venom

Venom from stinging or biting insects such as Hymenoptera (ants, bees, and wasps) or Triatominae (kissing bugs) may cause anaphylaxis in susceptible people.[7][27][28] Previous systemic reactions, which are anything more than a local reaction around the site of the sting, are a risk factor for future anaphylaxis;[29][30] however, half of fatalities have had no previous systemic reaction.[31]

Risk factors

People with atopic diseases such as asthma, eczema, or allergic rhinitis are at high risk of anaphylaxis from food, latex, and radiocontrast agents but not from injectable medications or stings.[3][8] One study in children found that 60% had a history of previous atopic diseases, and of children who die from anaphylaxis, more than 90% have asthma.[8] Those with mastocytosis or of a higher socioeconomic status are at increased risk.[3][8] The longer the time since the last exposure to the agent in question, the lower the risk.[12]

Pathophysiology

Anaphylaxis is a severe allergic reaction of rapid onset affecting many body systems.[5][6] It is due to the release of inflammatory mediators and cytokines from mast cells and basophils, typically due to an immunologic reaction but sometimes non-immunologic mechanism.[6]

Immunologic

In the immunologic mechanism, immunoglobulin E (IgE) binds to the antigen (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates FcεRI receptors on mast cells and basophils. This leads to the release of inflammatory mediators such as histamine. These mediators subsequently increase the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and cause heart muscle depression.[6][12] There is also an immunologic mechanism that does not rely on IgE, but it is not known if this occurs in humans.[6]

Non-immunologic

Non-immunologic mechanisms involve substances that directly cause the degranulation of mast cells and basophils. These include agents such as contrast medium, opioids, temperature (hot or cold), and vibration.[6][19] Sulfites may cause reactions by both immunologic and non-immunologic mechanisms.[32]

Diagnosis

Anaphylaxis is diagnosed on the basis of a person's signs and symptoms.[3] When any one of the following three occurs within minutes or hours of exposure to an allergen there is a high likelihood of anaphylaxis:[3]

    Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure causing symptoms

    Two or more of the following symptoms after a likely contact with an allergen:

        a. Involvement of the skin or mucosa
        b. Respiratory difficulties
        c. Low blood pressure
        d. Gastrointestinal symptoms

    Low blood pressure after exposure to a known allergen

Skin involvement may include: hives, itchiness or a swollen tongue among others. Respiratory difficulties may include: shortness of breath, stridor, or low oxygen levels among others. Low blood pressure is defined as a greater than 30% decrease from a person's usual blood pressure. In adults a systolic blood pressure of less than 90 mmHg is often used.[3]

During an attack, blood tests for tryptase or histamine (released from mast cells) might be useful in diagnosing anaphylaxis due to insect stings or medications. However these tests are of limited use if the cause is food or if the person has a normal blood pressure,[3] and they are not specific for the diagnosis.[17]

Classification

There are three main classifications of anaphylaxis. Anaphylactic shock is associated with systemic vasodilation that causes low blood pressure which is by definition 30% lower than the person's baseline or below standard values.[14] Biphasic anaphylaxis is the recurrence of symptoms within 1–72 hours with no further exposure to the allergen.[3] Reports of incidence vary, with some studies claiming as many as 20% of cases.[33] The recurrence typically occurs within 8 hours.[8] It is managed in the same manner as anaphylaxis.[7] Pseudoanaphylaxis or anaphylactoid reactions are a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation.[8][34] Non-immune anaphylaxis is the current term used by the World Allergy Organization[34] with some recommending that the old terminology no longer be used.[8]

[Jhanananda]

This is promising; however, I am not waiting for 10 years of double blind studies before the new drug is cleared.  Today I started wearing a respirator all day long to see if it reduces my chronic caugh, so far only a few hours into it, and I seem to be coughing less.
Scientists Think They've Found a Way to Stop Allergic Reactions Before They Happen

Researchers have been working to find more effective allergy treatments, and now they've discovered how a particular antibody can stop an allergic reaction from happening altogether.

When the body is exposed to an allergen, the immune system goes into overdrive producing ridiculous amounts of a specific type of antibody called immunoglobulin E (IgE). It's a large, Y-shaped molecule that attaches itself to the immune cells tasked with releasing invader-attacking chemicals.

These compounds - especially histamine - go on to produce the varied and miserable symptoms of an allergy, whether it's a runny nose and eyes, or the more serious anaphylactic reaction that accompanies severe food allergies or insect bites.

Allergy tablets typically target these immune system compounds or their receptors, therefore preventing or at least easing the allergy symptoms. But if we target IgE itself, there's a chance to prevent the allergic reaction from even taking place.

A team led by scientists at Aarhus University in Denmark has now discovered a mechanism through which a particular anti-IgE antibody can make this miracle happen.

This new antibody, called 026 sdab, was first derived from llamas, and is akin to a range of such molecules discovered in camelid species and cartilaginous fishes.

The way 026 sdab works in the human body is by preventing IgE from getting to two specific types of immune receptors - CD23 and FceRI - and thus stopping the allergic reaction before it even starts.

There's already one anti-IgE therapy on the market, called omalizumab - it's approved in over 90 countries for the treatment of stubborn cases of allergic asthma, but isn't always effective.

According to the team, 026 sdab is a much smaller antibody than what's currently available or in development. It's also easier to produce, and is "extremely stable", which means it doesn't have to be injected like omalizumab does.

[Jhanananda]

Omalizumab
Omalizumab, sold under the trade name Xolair, is a medication originally designed to reduce sensitivity to allergens. It has been used to try to control severe allergic asthma, which does not respond to high doses of corticosteroids. It has been approved for treating people 12 years and older with severe or moderate to severe allergic asthma in more than 90 countries, since its first of such approval in 2002 in Australia. Omalizumab was approved in March 2014 in the European Union and the U.S.A. and in about 10 other countries for treating patients 12 years and above with chronic spontaneous urticaria (CSU) (also referred to as chronic idiopathic urticaria or CIU), which cannot be treated with H1-antihistamines. CSU is not an allergic disease.

Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglobulin E (IgE) in the blood and interstitial fluid and to membrane-bound form of IgE (mIgE) on the surface of mIgE-expressing B lymphocytes.[1] Unlike an ordinary anti-IgE antibody, it does not bind to IgE that is already bound by the high affinity IgE receptor (FcεRI) on the surface of mast cells, basophils, and antigen-presenting dendritic cells.[2]

IgE is commonly involved in type I hypersensitivity, which manifests in the most common allergic diseases. It has been estimated that as high as 20 to 40% of the populations who live a western lifestyle in economically advanced countries are affected by allergy and seek medical help.[3] In the U.S., 8% of adults and 10% of children have asthma.[4] Allergy occurs more frequently in individuals with higher serum IgE levels, though some allergic individuals have very low serum IgE, and some people with very high IgE have no allergic problems.[2]

Allergic asthma

Omalizumab received approval by the U.S. Food and Drug Administration (FDA) in 2003 for treating patients 12 years and older with moderate to severe allergic asthma.[5] It has also received approval in many other countries for treating patients 12 years and older with severe, persistent allergic asthma. Omalizumab was approved by the European Union in 2009 for treating patients 6 to 12 years old with severe, persistent allergic asthma. Thus, its primary use is for patients mostly with severe, persistent allergic asthma, uncontrollable with oral or injectable corticosteroids.[6] Those patients have already failed step I to step IV treatments and are in step V of treatment. Such a treatment scheme is consistent with the widely adopted guidelines for the management and prevention of asthma, issued by Global Initiative of Asthma (GINA), which was a medical guidelines organization launched in 1993 in collaboration with the National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and the World Health Organization.[7] The efficacy is more evident among severe asthmatics than among those with moderately severe disease. The response rates among treated severe "allergic" asthma patients are 60-80% or higher, probably depending on the patient screening procedures used by the various clinical groups of different specialties. In real-life clinical practice of 142 and 195 patients in Italy and Germany, respectively, 77 to 79% of patients or physicians gave a response of “excellent or good” for GETE (global evaluation of treatment effectiveness) scale after being treated with omalizumab for four months.[8][9] Because 20 to 30% of adult asthma cases are not related to allergy,[9] a reliable way to identify treatable patients has been a subject of considerable research interest.[10][11] The primary benefits for the responding patients are reduced numbers of exacerbations, improved lung function, reduced numbers of emergency visits to the doctors, reduced days of hospitalization, and increased quality of life measurements.[8][9] The other major benefit is that most responding patients can reduce or spare entirely the use of corticosteroids, which cause multiple serious side effects, when used at high doses for extended periods.[12]

Due to the requirement for long-term administration and hence the high cost of an omalizumab treatment regimen, and to the concern over long-term safety, treatment is not yet very common, especially in developing countries where medical funds are relatively scarce. Another barrier to wide use is its injectable dosage form, which requires the patient to visit a physician's office or clinic every 2 to 4 weeks during treatment. In August 2010, the National Institute for Clinical Excellence (NICE) in the United Kingdom ruled that omalizumab should not be prescribed on the National Health Service (NHS) to children under 12, causing widespread condemnation from asthma charities.[13] NICE concluded that the high costs of the compound, over £250 per vial, did not represent a sufficiently high increase in quality of life. However, on March 7, 2013, NICE issued “final draft guidance” about the allowance of omalizumab. It recommended the drug as an option for treating severe, persistent allergic asthma in adults, adolescents and children following additional analyses and submission of a patient access scheme (PAS) by Novartis, the manufacturer.[14] Some immunologists have also suggested that because IgE may be a natural defense against parasitic diseases, treatment should not be recommended when living in environments where the presence of parasites is common.
Chronic spontaneous urticaria

Xolair was approved in March 2014 in the European Union and the U.S.A. and in about 10 other countries for treating patients 12 years and above with chronic spontaneous urticaria (also called chronic idiopathic urticaria), which cannot be treated with elevated doses of H1-antihistamines.

Chronic urticaria affect about 0.5 to 1% of the world population and among those patients, two thirds have CSU, and among them, about half cannot be adequately treated even with high doses (4 times regular doses) of H1-antihistamines.[15][16] Since CSU is not an allergic disease and does not obviously involve IgE, how omalizumab effectively treats CSU is currently a hotly pursued research subject. The serum concentrations of IgE in CSU patients are generally much lower than those in patients with allergic asthma.
Adverse effects

The main adverse effect is anaphylaxis (a life-threatening systemic allergic reaction), with a rate of occurrence of 1 to 2 patients per 1,000.[6][17] Like other protein and antibody drugs, omalizumab also causes anaphylaxis, although at a relatively low frequency among antibody drugs. The allergic reaction is probably not due to the binding characteristics of the antibody drug, but to the protein nature of the antibody[citation needed]. The patients who use omalizumab are generally highly allergic. Thus, even though the drug is administered with the purpose to suppress allergy (including anaphylactic reactions), it does not work immediately after injection.

It also increases the risk of strokes and heart disease by a small amount.[18]

IgE may play an important role in the immune system's recognition of cancer cells.[19] Therefore, indiscriminate blocking of IgE-receptor interaction with omalizumab may have unforeseen risks. The data pooled in 2003 from the earlier phase I to phase III clinical trials showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.2%).[6] To clarify this imbalance, a more recent study was performed based on pooled analysis using much more comprehensive data from 67 phase I to IV clinical trials. The prespecified primary analysis assessed the incidence of primary malignancy in 32 randomized, double-blind, placebo-controlled (RDBPC) trials. In this analysis, there were 11,459 unique patients in all clinical trials (7,789 received omalizumab). The primary analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254 omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence rates per 1,000 patient-years of observation time for omalizumab- and placebo-treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94), respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary malignancies were of varying histologic type and occurred in a number of different organ systems; no cluster of histologies was identified. The study thus concluded that in this pooled analysis no association was observed between omalizumab treatment and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data suggest that a causal relationship between omalizumab therapy and malignancy is unlikely.[20]

Concerns were raised earlier about possible induction of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), a rare form of systemic vasculitis associated with asthma, in patients receiving the drug.[21] A retrospective review, which identified and analyzed cases of Churg-Strauss syndrome using the Novartis Argus global drug safety database for omalizumab in asthma patients, has indicated that Churg-Strauss syndrome may develop in patients who have an underlying eosinophilic disorder that is unmasked by the withdrawal of corticosteroids, which is common among patients receiving this treatment.[22]

20 to 40% of the populations who live a western lifestyle in economically advanced countries are affected by allergy

The above seems significant, and suggests industrial pollution as a cause.

[Jhanananda]

To understand how allergies work, and how to prevent an allergic reaction, we need to understand: Pollen and spores, and Terpene.

Pollen
The smallest pollen grain, that of the forget-me-not (Myosotis spp.),[which?] is around 6 µm (0.006 mm) in diameter.[citation needed] Wind-borne pollen grains can be as large as about 90–100 µm.[2]

Allergy to pollen
Nasal allergy to pollen is called pollinosis, and allergy specifically to grass pollen is called hay fever. Generally, pollens that cause allergies are those of anemophilous plants (pollen is dispersed by air currents.) Such plants produce large quantities of lightweight pollen (because wind dispersal is random and the likelihood of one pollen grain landing on another flower is small), which can be carried for great distances and are easily inhaled, bringing it into contact with the sensitive nasal passages.

In the US, people often mistakenly blame the conspicuous goldenrod flower for allergies. Since this plant is entomophilous (its pollen is dispersed by animals), its heavy, sticky pollen does not become independently airborne. Most late summer and fall pollen allergies are probably caused by ragweed, a widespread anemophilous plant.[13]

Arizona was once regarded as a haven for people with pollen allergies, although several ragweed species grow in the desert. However, as suburbs grew and people began establishing irrigated lawns and gardens, more irritating species of ragweed gained a foothold and Arizona lost its claim of freedom from hay fever.

Anemophilous spring blooming plants such as oak, birch, hickory, pecan, and early summer grasses may also induce pollen allergies. Most cultivated plants with showy flowers are entomophilous and do not cause pollen allergies.

The number of people in the United States affected by hay fever is between 20 and 40 million,[14] and such allergy has proven to be the most frequent allergic response in the nation. There are certain evidential suggestions pointing out hay fever and similar allergies to be of hereditary origin. Individuals who suffer from eczema or are asthmatic tend to be more susceptible to developing long-term hay fever.[15]

In Denmark, decades of rising temperatures cause pollen to appear earlier and in greater numbers, as well as introduction of new species such as ragweed.[16]

The most efficient way to handle a pollen allergy is by preventing contact with the material. Individuals carrying the ailment may at first believe that they have a simple summer cold, but hay fever becomes more evident when the apparent cold does not disappear. The confirmation of hay fever can be obtained after examination by a general physician.[17]
Treatment
Main article: Allergic rhinitis § treatment

Antihistamines are effective at treating mild cases of pollinosis, this type of non-prescribed drugs includes loratadine, cetirizine and chlorpheniramine. They do not prevent the discharge of histamine, but it has been proven that they do prevent a part of the chain reaction activated by this biogenic amine, which considerably lowers hay fever symptoms.

Decongestants can be administered in different ways such as tablets and nasal sprays.

Allergy immunotherapy (AIT) treatment involves administering doses of allergens to accustom the body to pollen, thereby inducing specific long-term tolerance.[18] Allergy immunotherapy can be administered orally (as sublingual tablets or sublingual drops), or by injections under the skin (subcutaneous). Discovered by Leonard Noon and John Freeman in 1911, allergy immunotherapy represents the only causative treatment for respiratory allergies.

spores
In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, fungi and protozoa.[1] Bacterial spores are not part of a sexual cycle but are resistant structures used for survival under unfavourable conditions.

Terpene
Terpenes (/ˈtɜːrpiːn/) are a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers,[1] and by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeteria. They often have a strong odor and may protect the plants that produce them by deterring herbivores and by attracting predators and parasites of herbivores.[2][3] The difference between terpenes and terpenoids is that terpenes are hydrocarbons, whereas terpenoids contain additional functional groups.

They are the major components of resin, and of turpentine produced from resin. The name "terpene" is derived from the word "turpentine". In addition to their roles as end-products in many organisms, terpenes are also major biosynthetic building blocks within nearly every living creature. Steroids, for example, are derivatives of the triterpene squalene.

Terpene Toxicity
Background

Terpenes are natural products derived from plants that have medicinal properties and biological activity. Terpenes may be found in cleaning products, rubefacients, aromatherapy, and various topical preparations. Terpenes may exist as hydrocarbons or have oxygen-containing compounds such as ketone or aldehyde groups (terpenoids).

Pathophysiology

Terpenes are local irritants and, thus, are capable of causing GI signs and symptoms. CNS manifestations may range from an altered mental status to seizures to coma. Aspiration is a particular concern and can result in fatalities and long-term complications.

Absorption begins in the oral cavity and is rapid as evidenced by the early onset of toxicity in significant ingestions. Terpenes are metabolized through cytochrome P450 and are excreted as conjugated metabolites by the kidney.

[Jhanananda]

I have had an allergy caused lung infection for several weeks now.  To deal with air-borne allergies it seems to me that just wearing a respirator would eliminate the allergen, so that anti-histamines may not be needed.  Last week I purchased a respirator with a p95 filter on it.  My health has improved since.

I chose the P95 filter because it is meant to filter out both particles, as well as hydrocarbons, such as terpenes.

[Anon]

Are you able to enter jhana despite your illness?

[Jhanananda]

Yes.

[Jhanananda]

I developed a lung infection in mid January.  My allergist has sent me in for a lot of tests.  He tested me for TB, it was negative.  He tested me for Valley Fever, it too was negative. However, he found I tested positive Aspergillosis.

Definition of Aspergillosis
Aspergillosis is an infection caused by Aspergillus, a common mold (a type of fungus) that lives indoors and outdoors. Most people breathe in Aspergillus spores every day without getting sick. However, people with weakened immune systems or lung diseases are at a higher risk of developing health problems due to Aspergillus. The types of health problems caused by Aspergillus include allergic reactions, lung infections, and infections in other organs.  There are different types of aspergillosis. Some types are mild, but some of them are very serious.

Types of aspergillosis

    Allergic bronchopulmonary aspergillosis (ABPA): Aspergillus causes inflammation in the lungs and allergy symptoms such as coughing and wheezing, but doesn’t cause an infection.2
    Allergic Aspergillus sinusitis: Aspergillus causes inflammation in the sinuses and symptoms of a sinus infection (drainage, stuffiness, headache) but doesn’t cause an infection.3
    Aspergilloma: also called a “fungus ball.” As the name suggests, it is a ball of Aspergillus that grows in the lungs or sinuses, but usually does not spread to other parts of the body.4
    Chronic pulmonary aspergillosis: a long-term (3 months or more) condition in which Aspergillus can cause cavities in the lungs. One or more fungal balls (aspergillomas) may also be present in the lungs.5
    Invasive aspergillosis: a serious infection that usually affects people who have weakened immune systems, such as people who have had an organ transplant or a stem cell transplant. Invasive aspergillosis most commonly affects the lungs, but it can also spread to other parts of the body.
    Cutaneous (skin) aspergillosis: Aspergillus enters the body through a break in the skin (for example, after surgery or a burn wound) and causes infection, usually in people who have weakened immune systems. Cutaneous aspergillosis can also occur if invasive aspergillosis spreads to the skin from somewhere else in the body, such as the lungs.6

Symptoms of Aspergillosis

The different types of aspergillosis can cause different symptoms.1

The symptoms of allergic bronchopulmonary aspergillosis (ABPA) are similar to asthma symptoms, including:

    Wheezing
    Shortness of breath
    Cough
    Fever (in rare cases)

Symptoms of allergic Aspergillus sinusitis2 include:

    Stuffiness
    Runny nose
    Headache
    Reduced ability to smell

Symptoms of an aspergilloma (“fungus ball”)3 include:

    Cough
    Coughing up blood
    Shortness of breath

Symptoms of chronic pulmonary aspergillosis4,5 include:

    Weight loss
    Cough
    Coughing up blood
    Fatigue
    Shortness of breath

Invasive aspergillosis1 usually occurs in people who are already sick from other medical conditions, so it can be difficult to know which symptoms are related to an Aspergillus infection. However, the symptoms of invasive aspergillosis in the lungs include:

    Fever
    Chest pain
    Cough
    Coughing up blood
    Shortness of breath
    Other symptoms can develop if the infection spreads from the lungs to other parts of the body.

Sources of Aspergillosis

 Aspergillus lives in the environment

Aspergillus, the mold (a type of fungus) that causes aspergillosis, is very common both indoors and outdoors, so most people breathe in fungal spores every day. It’s probably impossible to completely avoid breathing in some Aspergillus spores. For people with healthy immune systems, breathing in Aspergillus isn’t harmful. However, for people who have weakened immune systems, breathing in Aspergillus spores can cause an infection in the lungs or sinuses which can spread to other parts of the body.
I’m worried that the mold in my home is Aspergillus. Should someone test the mold to find out what it is?

No. Generally, it’s not necessary to identify the species of mold growing in a home, and CDC doesn’t recommend routine sampling for molds. For more information about indoor mold, including cleanup and remediation recommendations, please visit CDC’s Basic Facts about Mold web page.
Types of Aspergillus

There are approximately 180 species of Aspergillus, but fewer than 40 of them are known to cause infections in humans. Aspergillus fumigatus is the most common cause of human Aspergillus infections. Other common species include A. flavus, A. terreus, and A. niger.

[Jhanananda]

A year and a half ago I found a dead tree with a large colony of oyster mushrooms growing on it.  I have studied foraging behavior through foraging.  I took up foraging for wild edible mushrooms about 12 years ago, when I lived in the Inyo National Forest.  So, I looked up the mushroom in my Audubon Mushroom guide, and confirmed that it was in deed oyster mushroom.  So, I extracted as much usable oyster mushroom.  It was rainy season here, so I thinly sliced the mushrooms, and put them into cloth bags, and hung them from hooks inside my van.  Within days I had a massive lung infection.  A friend here had been looking into commercially growing mushrooms, so when he heard that I had been drying oyster mushrooms in my van, and saw that I had a lung infection, then he told me about "mushroom worker's lung."

Hypersensitivity pneumonitis
Hypersensitivity pneumonitis (HP; also called allergic alveolitis or extrinsic allergic alveolitis, EAA) is an inflammation of the alveoli within the lung caused by hypersensitivity to inhaled organic dusts. Sufferers are commonly exposed to the dust by their occupation or hobbies.

Signs and symptoms

Hypersensitivity pneumonitis (HP) is categorized as acute, subacute, and chronic based on the duration of the illness.[1]
Acute

In the acute form of HP, symptoms may develop 4–6 hours following heavy exposure to the provoking antigen. Symptoms include fever, chills, malaise, cough, chest tightness, dyspnea, rash, swelling and headache. Symptoms resolve within 12 hours to several days upon cessation of exposure.[2]

Acute HP is characterized by poorly formed noncaseating interstitial granulomas and mononuclear cell infiltration in a peribronchial distribution with prominent giant cells.[2]

On chest radiographs, a diffuse micronodular interstitial pattern (at times with ground-glass density in the lower and middle lung zones) may be observed. Findings are normal in approximately 10% of patients." In high-resolution CT scans, ground-glass opacities or diffusely increased radiodensities are present. Pulmonary function tests show reduced diffusion capacity of lungs for carbon monoxide (DLCO). Many patients have hypoxemia at rest, and all patients desaturate with exercise.[2] Extrinsic allergic alveolitis may eventually lead to Interstitial lung disease.[3]
Subacute

Patients with subacute HP gradually develop a productive cough, dyspnea, fatigue, anorexia, weight loss, and pleurisy. Symptoms are similar to the acute form of the disease, but are less severe and last longer. On chest radiographs, micronodular or reticular opacities are most prominent in mid-to-lower lung zones.[2] Findings may be present in patients who have experienced repeated acute attacks.

The subacute, or intermittent, form produces more well-formed noncaseating granulomas, bronchiolitis with or without organizing pneumonia, and interstitial fibrosis.[2]
Chronic

In chronic HP, patients often lack a history of acute episodes. They have an insidious onset of cough, progressive dyspnea, fatigue, and weight loss. This is associated with partial to complete but gradual reversibility. Avoiding any further exposure is recommended. Clubbing is observed in 50% of patients. Tachypnea, respiratory distress, and inspiratory crackles over lower lung fields often are present.[2]

On chest radiographs, progressive fibrotic changes with loss of lung volume particularly affect the upper lobes. Nodular or ground-glass opacities are not present. Features of emphysema are found on significant chest films and CT scans.[2]

Chronic forms reveal additional findings of chronic interstitial inflammation and alveolar destruction (honeycombing) associated with dense fibrosis. Cholesterol clefts or asteroid bodies are present within or outside granulomas.[2]

In addition, many patients have hypoxemia at rest, and all patients desaturate with exercise.
Pathophysiology

Hypersensitivity pneumonitis involves inhalation of an antigen. This leads to an exaggerated immune response (hypersensitivity). Type III hypersensitivity and type IV hypersensitivity can both occur depending on the cause.[4]

[Jhanananda]

Last Friday I moved the ice-chest out of my van and discovered a large mat of fungi growing under it, which suggests the source of the fungi that is killing me, is in my van.  It is probably Aspergillus.  And, I bet it is common in Prescott.

Last Friday I moved the ice-chest out of my van and discovered a large mat of fungi growing under it, which suggests the source of the fungi that is killing me, is in my van.  It is probably Aspergillus.  And, I bet it is common in Prescott.

My new host here, has offered a trailer for me to move into.  I plan to do so today, to reduce further exposure to Aspergillus.

Also, two toes on my right foot have been in extreme pain for the last 24 hours.  During my morning shower today I found one swollen and the other white.  They may have to be amputated soon, but I am going to try soaking them in hot water and salt, and massaging them regularly to see if I can rehab them.  It is the consequence of diabetic neuropathy.Peripheral neuropathy

Peripheral neuropathy
Peripheral neuropathy (PN) is damage to or disease affecting nerves, which may impair sensation, movement, gland or organ function, or other aspects of health, depending on the type of nerve affected. Common causes include systemic diseases (such as diabetes or leprosy), hyperglycemia-induced glycation,[1][2][3] vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (Ciprofloxacin, Levaquin, Avelox etc.), traumatic injury, including ischemia, radiation therapy, excessive alcohol consumption, immune system disease, Coeliac disease, or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause).[4][5][6] In conventional medical usage, the word neuropathy (neuro-, "nervous system" and -pathy, "disease of")[7] without modifier usually means peripheral neuropathy.

Neuropathy affecting just one nerve is called "mononeuropathy" and neuropathy involving nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply "polyneuropathy". When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called "mononeuritis multiplex", "multifocal mononeuropathy", or "multiple mononeuropathy".[4][5][6]

Peripheral neuropathy may be chronic (a long-term condition where symptoms begin subtly and progress slowly) or acute (sudden onset, rapid progress, and slow resolution). Acute neuropathies demand urgent diagnosis. Motor nerves (that control muscles), sensory nerves, or autonomic nerves (that control automatic functions such as heart rate, body temperature, and breathing) may be affected. More than one type of nerve may be affected at the same time. Peripheral neuropathies may be classified according to the type of nerve predominantly involved, or by the underlying cause.[4][5][6]

Neuropathy may cause painful cramps, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or skin allodynia (severe pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally.[4][5][6]