Objective Tests

a)

Spirometry (FEV1;FVC;FEV1/FVC ratio)

b)

PEF [peak expiratory flow rate]: as opposed to formal spirometry (which is performed in a physician's office), the patient can use a home peak flow meter (hand-held device) to check his/her peak flow readings on a regular basis.

c)

Methacholine challenge: research tool in which a chemical irritant substance is inhaled into the airways in a controlled fashion to induce asthma symptoms. It can be used to diagnose asthma, characterize the severity of asthma, and/or assess the patient's response to treatment.

d)

Allergen challenge testing: research tool in which allergen is introduced into the airways in a controlled fashion to reproduce allergen-induced asthma symptoms and characterize the patient's allergic response and response to treatment.

e)

Exercise challenge: research tool in which intense exercise is used to trigger asthma symptoms, spirometry tests before and after to provide evidence of exercise-induced bronchoconstriction.

a)

Medications Long term control medications: Long term control medications are used daily to achieve and maintain control of persistent asthma. The most effective are those that attenuate the underlying inflammation characteristic of asthma. Long term control medications include corticosteroids, cromolyn sodium and nedocromyl, immunomodulators, leukotriene modifiers, long-acting bronchodilators and methylxanthines. https://www​.nhlbi.nih​.gov/files/docs/guidelines/asthsumm.pdf

b)

Quick-relief medication: Quick-relief medications are used to treat acute symptoms and exacerbations. They include the following: short-acting beta agonists (SABA), anticholinergics and systemic corticosteroids. https://www​.nhlbi.nih​.gov/files/docs/guidelines/asthsumm.pdf

c)

Systemic corticosteroids: There are potent anti-inflammatory medications, usually used in oral forms, for treatment of asthma. They can be used in the short term for quick relief or long term as long term control medications. https://www​.nhlbi.nih​.gov/files/docs/guidelines/asthsumm.pdf

d)

Placebo: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. https://www​.drugs.com​/article/placebo-effect.html

Medications for asthma care

https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/full-report

a)

Corticosteroids: anti-inflammatory medications that reduce airway hyperresponsiveness, inhibit inflammatory cell migration and activation, and block late phase reaction to allergen

1. Inhaled corticosteroid (ICS): beclomethasone dipropionate (QVAR, Vanceril, Beclovent)), budesonide (Pulmicort), flunisolide (Aerobid), mometasone, fluticasone propionate (Flovent), triamcinolone acetonide (Azmacort)
2. Systemic corticosteroids: Prednisone, Prednisolone (Prelone, Pediapred), Methylprednisolone (Medrol, Solu-Medrol), Triamcinolone (Kenalog).

b)

Leukotriene antagonist (LTRA): A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.

Montelukast (Singulair), zafirlukast (Accolate), zileuton (Zyflo)

c)

Beta₂ agonists; Inhaled bronchodilators that relax smooth muscle.

1. Short acting beta agonists (SABAs) - duration of bronchodilation of less than 12 hours after a single dose; albuterol, levalbuterol, pirbuterol.
2. Long acting beta agonist (LABAs) – duration of bronchodilation of at least 12 hours after a single dose; salmeterol and folmoterol

d)

Cromolyn (Cromolyn sodium): A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.

e)

Anticholinergics: Inhibit muscarinic cholinergic receptors and reduce vagal tone in the airway. Ipatropium is used as an alternative to SABAs or as added treatment.

f)

Methylxantines: bronchodilators that relax smooth muscle. Sustained-release theophylline is a mild to moderate bronchodilator used as adjunctive therapy.

g)

Immunomodulators: Omalizumab is an anti-IgE monoclonal antibody, therefore it prevents binding of IgE to its receptor in basophils and mast cells (prevents sensitization)

Efficacy measures

a)

Asthma symptoms: Recorded self-assessment of asthma signs and symptoms through validated scores. Validated scores included in this review are ACT, ACQ and P-ACT http://www​.thoracic.org​/members/assemblies​/assemblies/srn/questionaires/act.php

b)

Medication use: Need of daily medications. Reduction in long term control medication and quick relief medication.

c)

Quality of life (QOL): Asthma Quality of Life Questionnaire (AQLQ): There are 32 questions in the AQLQ addressing 4 domains (symptoms, activity limitation, emotional function and environmental stimuli). The activity domain contains 5 ‘patient-specific’ questions. This allows patients to select 5 activities in which they are most limited and these activities will be assessed at each follow-up. Patients are asked to think about how they have been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all - 1 = severely impaired). The overall AQLQ score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains. (Includes strenuous activities (such as hurrying, exercising, running upstairs, sports), moderate activities (such as walking, housework, gardening, shopping, climbing stairs), social activities (such as talking, playing with pets/children, visiting friends/relatives), work-related activities, and sleeping. http://www​.thoracic.org​/members/assemblies​/assemblies/srn/questionaires/aqlq.php

Mechanistic Terms

a)

Immunoglobulins (Ig): Multi-subunit proteins which function in immunity. They are produced by B lymphocytes from the immunoglobulins genes. They are comprised of two heavy chains (immunoglobulins heavy chains) and two light chains (immunoglobulins light chains) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms includes monomeric or polymeric forms, and transmembrane forms (B-Cell antigen receptors) or secreted forms (antibodies). They are divided by the amino acid sequence of their heavy chains into five classes; Immunoglobulin A (IgA), Immunoglobulin D (IgD), Immunoglobulins E (IgE), Immunoglobulin G (IgG), Immunoglobulin M (IgM), and various subclasses.

1. IgG: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG4, IgG2A, IgG2B.
2. IgE: An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity.
3. All other immunologic parameters, such as T-Lymphocytes (Lymphocytes responsible for cell-mediated immunity), cytokines (IL4/IL5/IL10/etc, non-antibody proteins that act as intercellular mediators) are not included as outcomes in this review.

b)

Sensitization: chain of cellular responses to induce an allergic response to a specific allergen. The allergen causes a chain of immunological responses; development of specific B and T cells, differentiation and clonal expansion of specific T-helpers and production of cytokines, with final induction of IgE production, and demonstrating a positive allergy skin test or positive specific IgE testing to that allergen. http://www​.nature.com​/nri/journal/v6/n10/fig_tab/nri1934_F1​.html

• Monosensitized: Patients who tested positive to only one allergen (or one family of related allergens) after being tested with a panel of allergens
• Polysensitized: Patients who tested positive to multiple allergens after being tested with a panel of allergens

Safety terms

http://osp.od.nih.gov/sites/default/files/resources/Reporting_Guidelines.pdf

a)

Adverse events (AE): An injury caused by medical management–rather than by the underlying disease–which prolongs hospitalization, produces a disability, or both. Etiology: Drug effects, wound infections, technical complications, negligence, diagnostic mishaps, therapeutic mishaps, and events occurring in the emergency room.

b)

An adverse event is any undesirable experience associated with the use of a medical product in a patient. (Food and Drug Administration, 2009: http://www​.fda.gov/Safety​/MedWatch/HowToReport/ucm053087.htm)

c)

Serious adverse events (SAE): The event is serious and should be reported when the patient outcome is: death, life-threatening, hospitalization (initial or prolonged), disability, congenital anomaly, or requires intervention to prevent permanent impairment or damage. (Food and Drug Administration, 2009)

d)

When a particular condition causes the immune system to overreact, it is referred to as hypersensitivity reaction that triggers the production of IgE. These reactions may be damaging, uncomfortable, or occasionally fatal. https://www​.aaaai.org​/conditions-and-treatments​/conditions-dictionary​/hypersensitivity-reactions

e)

Anaphylaxis: An acute hypersensitivity reaction (Type I IgE mediated allergic immediate reaction) due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. http://www​.worldallergy​.org/professional​/allergic_diseases_center​/anaphylaxis/anaphylaxissynopsis​.php