Agents encountered in the work place

• Flour dust (Bakers)

• Hay mold (Farmers)

• Formaldehyde, western cedar, dimethylethanolamine, anhydrides (Plastics, rubber & wood workers)

• Arabic gum (Printers)

• Azo dyes, anthraquinones, ethylenediamine, toluene diisocyantes, polyvinyl chloride (Chemical workers)

¹ Allergens

• Airborne pollens (e.g. Natural Ragweed Pollen Domes)

  House-dust mites

  Animal Dander (image from the American Association of Allergy, Asthma and Immunology)

• Allergic asthma requires an IGE response 

  • The IGE response is determined by T- and B lymphocytes.

    • Central to the processes is the interaction of antigen with mast cell-bound IgE molecules.

    • Anatomically, airway epithelium and submucosa include dendritic cells which process antigen. 

  • Dendritic cells, following uptake of antigen, move to local lymph nodes, there presenting material to T-cell receptors. 

  • In some circumstances (perhaps genetically determined) antigen interaction with naive T cells (T_H0) in the presence of IL-4 results in T_H0 cell differentiation to a T_H2 cells. 

    • This process, while facilitating asthma inflammation, also promotes B lymphocyte transformation from IgG and IgM production to IgE production. 

  • Following sensitization due to prolonged antigen exposure, very small amounts of antigen can produce significant worsening of the chronic underlying disease (asthma). 

• The central role of immune processes is reflected in the causal relationship in asthma in about 33% of all cases with contributory involvement in probably another 33% of cases. 

  • Although allergic asthma is typically seasonal, nonseasonal asthma can result from continued exposure to animal danders, dust mites, molds, etc. 

• Antigen exposure can induce an immediate airway obstruction response within the minutes timeframe with fairly rapid resolution.

  • However, in 30%-50% of cases, a late reaction which is another bronchoconstrictive event, may occur from 5-10 hours later. Sometimes only this late reaction is observed. 

  • The initial response to inhale allergen probably depends on antigen-Ab interactions on pulmonary mast cells with subsequent rapid release of mediators.

  • ⁵Dendritic Cell (Orange)

     

¹ Drugs as stimulatory with respect to the Asthmatic Response

• Aspirin

• Nonsteroidal anti-inflammatory agents (NSAIDS) COX; COX-2 inhibitors (e.g. Valdecoxib (Bextra))

  • Arthrotec (diclofenac/ misoprostol)

  • Celecoxib (Celebrex)

  • Diclofenac (Voltaren, Cataflam)

  • Diflunisal (Dolobid)

  • Etodolac (Lodine)
    Flurbiprofen (Ansaid)

  • Ibuprofen (Motrin)

  • Indomethacin

  • Ketoprofen (Orudis)

  • Ketorolac (Toradol)

  • Nabumetone (Relafen)

  • Naproxen (Naprosyn)

  • Piroxicam (Feldene)

  • Rofecoxib (Vioxx)

  • Salsalate (Disalcid)

  • Sulindac (Clinoril)

• Sulfites (preservative)

• Benzalkonium chloride (preservative/detergent)

• -adrenergic receptor antagonists, e.g. propranolol, metoprolol, atenolol, timolol

  • Propranolol (Inderal),

  • ¹ Acute asthma attacks may be induced by certain drugs, the most common of which include beta-adrenergic antagonists, sulfite-containing agents, aspirin, and coloring agents such as tartrazine.

    • Significant morbidity is associated with drug-induced bronchial constriction with death having been attributed to aspirin (or other nonsteroidal anti-inflammatory drugs) or beta adrenergic blocker ingestion. 

    • Aspirin-induced asthma appears to occur more frequently in adults relative to children. In aspirin sensitivity may begin with a vasomotor rhinitis (perennial) which leads to nasal polyps (hyperplastic rhinosinusitis).

¹ Environmental Factors

• Cold Air

• Fog

• Wood smoke; tobacco smoke

• Ozone

• Nitrogen dioxide

• Sulfur Dioxide

  • Asthma exacerbation may be induced by elevated concentrations of atmospheric pollutants/antigen's which may occur in particularly industrial or densely populated cities. 

  • Such accumulation is favored under certain weather conditions which create relatively stagnant air (thermal inversions). 

  • Asthmatic patients will be most severely affected, although the general population will also perceive respiratory effects. 

  • Ozone, nitrogen dioxide and sulfur dioxide have been identified as particularly important air pollutants in this regard, although sulfur dioxide requires both a high ventilatory rate and concentration. 

  • Airborne antigens (pollen) can seasonally rise to sufficient concentrations to markedly increased hospital admissions as well as death rates. Seasonal effects may be diminished impact by early  use of anti-inflammatory agents.

   

¹Occupational Factors

• Workplace factors

  • Flour dust (Bakers)

  • Hay mold (Farmers)

  • Formaldehyde, western cedar, dimethylethanolamine, anhydrides (Plastics, rubber & wood workers)

  • Arabic gum (Printers)

  • Azo dyes, anthraquinones, ethylenediamine, toluene diisocyantes, polyvinyl chloride (Chemical workers)

• Prolonged exposure in the workplace to a variety of substances may exacerbate asthma or induce an asthma attack. 

  • Bronchoconstriction may occur as a result of exposure to metal salts such as platinum, nickel or chrome. 

  • Other concerns involves wood or vegetable dust, certain drugs such as antibiotics, cimetidine, as well as industrial chemicals and plastics. 

  • Enzymes found in detergents and animal/insect dusts, serums, or secretions may also be provocative substances. 

  • These chemicals may also be found outside the workplace environment. 

• This type of airway obstruction appears to involve three possible underlying mechanisms

  • (1) the agent induces the formation of a specific IgE (resulting in an immediate, late, or dual immunological reaction)

  • (2) the agent reflexively or directly causes airway stimulation in the asthmatic patient

  • (3) the agent directly causes bronchoconstrictor substance liberation.

   

Infection

• Respiratory syncytial virus (RSV)

  "Human infant lung, post-mortem tissue: immunohistochemical staining for Respiratory Syncytial Virus (RSV) using NCL-RSV3. Note intense staining of infected luminal bronchial epithelial cells. Paraffin section." Image: © 2002 Novocastra Laboratories Ltd

•  

  ³Rhinovirus ("Rhinovirus 14, as solved by cryo-electron microscopy and image reconstruction)

• Influenza, parainfluenze

• Mycoplasma pneumoniae

• Acute worsening of asthma would be most likely due to respiratory infection. 

• The major factor is not bacterial or allergic responses to microorganisms would rather is a respiratory virus. 

  • In children the two most important viruses would be respiratory syncytial virus and parainfluenza virus. In the older child in adults, rhinovirus and influenza virus would be more common.

  •  An active respiratory tract infection is necessary to induce the asthma attack, going beyond colonization. In the individual whose asthma had been under control, such a respiratory infection can destabilize the condition for extended periods, e.g. weeks. 

  • A possible basis for this effect would be a viral-induced production of T-cell-derived cytokines which promote inflammatory cell infiltration into the airway.

   

Exercise: (or emotion)

• Stress

• Laughter

• Anxiety

• Exercise (dry, cold weather especially)

  • Acute asthma attacks are often provoked by exercise. 

  • Exercise, differing from other provocative factors, is not produce long-term effects and does not increase intrinsic airway reactivity. 

  • Bronchospasm can be induced by exercise in essentially every asthmatic patient and in some cases it is the only provocative act (at least initially) or exposure that causes asthmatic symptoms.

  • The severity of exercise-induced bronchoconstriction include ventilatory levels as well as humidity and temperature of the inspired air. 

    • The direction of the effect is that higher ventilation rates with reduced air temperature tend to promote greater obstructive responses. 

    • Running as opposed to walking causes a more severe asthmatic attack, even if the air temperature and humidity are the same in both cases. 

    • Furthermore for any given exertional task, cold air will tend to enhance the obstructive response and warm, humid air would likely reverse the effect. 

      • With respect to specific sports then, ice hockey & cross-country skiing our activities that would be more likely to cause an asthma attack then swimming inside, in a heated pool. 

    • A possibility, in terms of mechanism that might explain exercise-induced obstruction, involves thermal induction of hyperemia with microvascular engorgement of the bronchial wall.

   

Emotional Effects

• Psychological factors appear to interact with underlying asthma pathophysiology either to worsen or improve the disease state. 

• The psychological effects appear important to about 50 percent of patients. 

• Physiologically, airway caliber may be modulated through vagal efferent activity although endorphins may also contribute. 

• Patients may be "suggestible" with suggestion resulting in changes in adrenergic and cholinergic stimuli effects on airway. 

• Psychophysiological effects appear variable from patient to patient and possibly variable within a patient depending on the nature of the episode.