Asthma: An Overview


Naveen MR, Santhosh YL*

Department of Clinical Pharmacy, SAC College of Pharmacy, B.G.Nagra, India

*Corresponding Author E-mail:





Asthma is a clinical syndrome of unknown etiology characterized by three distinct components: (a) recurrent episodes of airway obstruction that resolve spontaneously or as a result of treatment: (b) exaggerated bronchoconstrictor response to stimuli that have little or no effect in nonasthmatic subjects, a phenomenon known as airway hyper responsiveness: and (c) inflammation of the airways as defined by a variety of criteria. Although airway obstruction is largely reversible, it is currently thought that changes in the asthmatic airway may be irreversible in some settings.1 The large burden it now imposes on patients, and the high health care costs have led to extensive research into its mechanisms and treatment. 2


The overall burden of asthma in India is estimated at more than 15 million patients. However, India is a vast country with immense geographical, economical, racial, religious and socio-political diversity. There are obvious differences in prevalence of disease and approach to management of health problems. It is an enormously difficult and costly proposition to collect national statistics on diagnosis and management of common diseases, as it requires coordination and cooperation between several centre spread across the country. Although some attempts have been made in the past, they suffer from several scientific drawbacks, the principle being a lack of uniformity of methodology and analysis of data. 3


The number of persons worldwide with asthma has increased to around 300 million, and may reach 400 million by 2025. The reasons for this dramatic increase are under investigation and may relate to adoption of Western lifestyles and urbanization.


About 1% of all disability-adjusted life years are lost due to asthma, and asthma accounts for 1 in every 250 deaths worldwide.4 In young children (0-10 years age), the risk of asthma is greater in boys than in girls, becomes about equal during puberty, and then is greater in women than in men. 5


Most deaths from asthma occur outside the hospital, and death is rare after hospitalization. The most common cause of death from asthma is inadequate assessment of the severity of airways obstruction by the patient or physician and inadequate therapy. The most common cause of death in hospitalized patients is also inadequate or inappropriate therapy. Thus the key to prevention of death from asthma, as advocated by the NAEPP, is education. 6



Asthma is defined as chronic inflammatory and increased airway responsiveness in which many cells and cellular elements play a role (mast cells, eosinophils, T lymphocytes, macrophages, neutrophils and epithelial cells), characterized by wheeze, cough, chest tightness and dyspnoea - is often reversible either spontaneously or with treatment. 7- 10


Asthma can be defined as a chronic inflammatory disorder of airways, in susceptible individuals: inflammatory symptoms are usually associated with wide spread but variable airflow obstruction and an increase in airway response to a variety of stimuli. Obstruction is often reversible either spontaneously or with treatment. 8


Clinical features:

Patients are aware of increasing chest tightness, wheezing and dyspnea that are often poorly or relived by their usual reliever inhaler.


Signs and symptoms:

In chronic asthma

Signs- Expiratory wheezing on auscultation, dry hacking cough or signs of atopy may occur

Symptoms- Patient may complain of episodes of dyspnea, chest tightness, coughing, wheezing or a whistling sound when breathing.


In acute asthma

Signs- Expiratory and inspiratory wheezing on auscultation, dry hacking cough, tachypnea, tachycardia pale or cyanotic skin, hyper inflated chest with intercostals and supraclavicular retractions, hypoxic seizures if very sever normal or slightly elevated temperature.


Symptoms- Patient is anxious in acute distress and complains of sever dyspnea, shortness of breath, chest tightness or burning. Patient is only able to speak a few words with each breath. 5



It is well recognized that expression of the disease is the result of a complex interrelationship between the presence and absence of genetic susceptibility and environmental influences. The difficulty in defining asthma relates to the multiple factors that trigger bronchospasm. 9 The examples of triggering factors are as shown in table number 1.



Asthma is an inflammatory process that involves multiple cell types and mediators has revolutionized the approach to prevention and management.11Inflammation is the underlying abnormality present in patients who have even mild asthma. The spectrum of inflammatory changes may include sub mucosal infiltration with activated lymphocytes and eosinophils, activation of mast cells, epithelial changes, and basement membrane thickening. These changes occur along a continuum from mild to severe asthma. In fatal asthma, additional findings of mucus plugging in airways, goblet cell hyperplasia, and smooth muscle hypertrophy/hyperplasia also usually are present and represent extension of the inflammatory continuum. 11


The gross pathology of asthmatic airways displays lung hyperinflation, smooth muscle hypertrophy, lamina reticularis thickening, mucosal edema, epithelial cell sloughing, cilia cell disruption, and mucus gland hyper secretion. Microscopically, asthma is characterized by the presence of increased numbers of eosinophils, neutrophils, lymphocytes, and plasma cells in the bronchial tissues, bronchial secretions, and mucus. Initially, there is recruitment of leukocytes from the bloodstream to the airway by activated CD4 T-lymphocytes. The activated T-lymphocytes also direct the release of inflammatory mediators from eosinophils, mast cells, and lymphocytes. In addition, the subclass 2 helper T-lymphocytes subset of activated T-lymphocytes produces interleukin (IL)-4, IL-5, and IL-13. IL-4 in conjunction with IL-13 signals the switch from IgM to IgE antibodies. The cross-linkage of two IgE molecules by allergen causes mast cells to degranulate, releasing histamine, leukotrienes, and other mediators that perpetuate the airway inflammation. IL-5 activates the recruitment and activation of eosinophils. The activated mast cells and eosinophils also generate their cytokines that help to perpetuate the inflammation. Regardless of the triggers of asthma, the repeated cycles of inflammation in the lungs with injury to the pulmonary tissues followed by repair may produce long-term structural changes ("remodeling") of the airways. This review will discuss in greater detail the relationships of inflammation and airway hyper responsiveness to the pathophysiology of asthma. 12


The figure 1 shows the pathophysiology of asthma is complex, with participation of several interacting inflammatory cells, resulting in acute and chronic inflammatory effects on the airway.2


Figure 1: Inflammatory cells interaction


TABLE NUMBER 1: Example of trigger factor that may cause asthma: 8




Pollens, moulds, house dust mites, animals(dander, saliva and urine)

Industrial chemicals

Manufacture of, for example, isocyanate containing paints, epoxy, resins, aluminium, hair sprays, penicillin’s and cimetidine


Aspirin, ibuprofen and other prostaglandin synthetase inhibitors, beta- adrenoceptor blockers


A rare cause but examples include nuts, food colouring, especially tartrazine, benzoic acid and sodium metabisulfite

Other industrial triggers

Wood or grain dust, colophony in solder, cotton dust, grain weevils and mites: also environmental pollutants such as cigarette smoke and sulphur dioxide


Cold air, exercise, hyperventilation, viral respiratory tract infection, emotion or stress


Classification of severity of asthma as shown in table number 2: 13

TABLE NUMBER 2: Classification of Asthma Severity:



Night time Symptoms

Lung Function




     Continual symptoms

     Limited physical activity

     Frequent exacerbations


     FEV1 or PEF ≤60% predicted

     PEF variability >30%




     Daily symptoms

     Daily use of inhaled short-acting beta2-agonist

     Exacerbations affect activity

     Exacerbations ≥2 times a week: may last days

>1 time a week

     FEV1 or PEF >60%–<80% predicted

     PEF variability >30%




     Symptoms >2 times a week but <1 time a day

     Exacerbations may affect activity

>2 times a month

     FEV1 or PEF ≥80% predicted

     PEF variability 20–30%




     Symptoms ≤2 times a week

     Asymptomatic and normal PEF between exacerbations

     Exacerbations brief (from a few hours to a few days): intensity may vary

≤2 times a month

     FEV1 or PEF ≥80% predicted

     PEF variability <20%

* The presence of one of the features of severity is sufficient to place a patient in that category. An individual should be assigned to the most severe grade in which any feature occurs. The characteristics noted in this figure are general and may overlap because asthma is highly variable.

Furthermore, an individual’s classification may change over time.

** Patients at any level of severity can have mild, moderate, or severe exacerbations. Some patients with intermittent asthma experience severe and life-threatening exacerbations separated by long periods of normal lung function and no symptoms.


Diagnosis and Clinical Findings: 9

The diagnosis of asthma is usually made on the basis of clinical history and objective measures of pulmonary function. It is as shown in table number 3.


TABLE NUMBER 3 : Differential Diagnosis of Asthma

Infants and Children


Allergic rhinitis and sinusitis
Foreign body in trachea or bronchus
Vocal cord dysfunction
Vascular rings or laryngeal webs
Laryngotracheomalacia, tracheal stenosis, or bronchostenosis
Enlarged lymph nodes or tumor
Viral bronchiolitis or obliterative bronchiolitis
Cystic fibrosis
Bronchopulmonary dysplasia
Heart disease

Aspiration from dysfunction of swallowing

Recurrent cough not due to asthma

Mechanism dysfunction or gastroesophageal reflux

Chronic obstructive pulmonary disease (chronic bronchitis or emphysema)
Congestive heart failure
Pulmonary embolism
Laryngeal dysfunction
Mechanical obstruction of the airways (tumors)
Pulmonary infiltration with eosinophilia
Cough secondary to drugs
Vocal cord dysfunction

(From National Asthma Education and Prevention Program. Expert panel report 2: guidelines for the diagnosis and management of asthma. Bethesda, MD: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, April 1997: Publication no 97–4051.)



Airflow is typically measured by spirometry or peak expiratory flow (Fig.2-A, B), and normal (predicted) values based on height, age, sex, and race are established. FEV1, the most commonly used spirometric evaluation of pulmonary function, consists of the volume of air expelled within the first second of forced expiration after maximal inhalation. It is normally >70% of the total volume of expired air (forced vital capacity (FVC)): however, in obstructive processes such as asthma, FEV1 is reduced, as is FVC (although to a lesser extent): therefore, the FEV1/FVC ratio is also reduced. Peak expiratory flow (PEF) is the maximal rate at which air is exhaled from the lungs with a forced expiratory maneuver: it correlates fairly well with FEV1, although for some patients, it does not correlate well with symptoms.

Bronchial Challenge:

Bronchial hyper responsiveness can be measured by inhalation challenge testing, with patients inhaling increasing doses of histamine or methacholine: the end point is the dose required to elicit a ≥20% fall in pulmonary function, typically FEV1. The provocative concentration or dose required for a 20% fall in FEV1 (PC20 or PD20) is inversely proportionate to bronchial hyper responsiveness: thus, a lower PD20 is indicative of greater reactivity (Fig.2-C, D). Not only can measures of bronchial hyper responsiveness be used for the diagnosis of asthma, but changes in PD20 over time may be useful for guiding therapy and gauging response to therapy.




FIGURE 2- A. Typical spirometry of normal and obstructed patients. Note the lower forced expiratory volume at 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio in the obstructed patient. B. Typical flow-volume loops of a normal and obstructed patient. Note the lower peak expiratory flow, increased lung volume, and typical “scooped out” expiratory curve in the obstructed patient. C. Typical immediate and late asthmatic responses seen following exposure to relevant allergen. Immediate asthmatic response (IAR) occurs within minutes, and late asthmatic response (LAR) occurs several hours after exposure. Patients may demonstrate an isolated IAR, an isolated LAR, or dual responses. D. Typical pulmonary function seen with histamine or methacholine challenge testing in normal and hyper responsive patients. The provocative concentration or dose of histamine or methacholine required to elicit a drop in FEV1 of 20% (PC20 or PD20) is inversely proportionate to bronchial hyper responsiveness.



Allergen prick skin testing is the most commonly used diagnostic test for atopy.

Skin testing can be performed on infants as young as 3 months of age. If the patient is unable to withhold oral antihistamines before skin testing is performed, or is otherwise not a candidate for skin testing


Chest X-Ray:

Chest radiographs (posterior-anterior) may be normal in mild disease: however, signs of air trapping (hyperinflation) are more often present with severe, chronic asthma. Radiographs may be more useful in younger children, particularly infants, to exclude alternative conditions that may be causing symptoms of reduced airflow such as pneumonia, cystic fibrosis, recurrent milk inhalation, congenital heart disease, or other congenital malformations.1, 2 Chest radiographs taken in the emergency department for patients with acute asthma add little to the medical management of these patients, except possibly for those with other complicating findings.


Management of Asthma:

The goals for successful management of asthma are to:

• Achieve and maintain control of symptoms

• Maintain normal activity levels, including exercise

• Maintain pulmonary function as close to normal as possible

• Prevent asthma exacerbations

• Avoid adverse effects from asthma medications

• Prevent asthma mortality 14


Non-pharmacological management:

There are numerous environmental, dietary and other triggers of asthma that avoiding these triggers will improve asthma and reduce the requirement for pharmacotherapy. This section distinguishes:

1.        Primary prophylaxis- interventions introduced before the onset of disease and designed to reduce its incidence.

2.        Secondary prophylaxis- interventions introduced after the onset of disease to reduce its impact.


Primary prophylaxis:

Ø  Aero allergen avoidance

Ø  Food allergen avoidance

Ø  Nutritional supplementation-fish oils (omega-3 poly unsaturated fatty acids)

Ø  Avoidance of tobacco smoke and other air pollutants

Ø  Immunotherapy

Ø  Immunization



Secondary non-pharmacological prophylaxis:

Ø  House dust mite avoidance (removal of carpets and toys from bed, high temperature washing of bed linen etc)

Ø  Other allergence ( animal allergens, fungal exposure etc)


Other environmental factors:

Ø  Smoking

Ø  Air pollution

Ø  Immunotherapy


Dietary manipulation:

Ø  Electrolytes

Ø  Fish oils/lipids

Ø  Antioxidants

Ø  Weight reduction in obese patients with asthma

Ø  Probiotics

Ø  immunizations


Complementary and alternative medicine:

Ø  Acupuncture

Ø  Air ionizers

Ø  Breathing exercise including yoga and the buteyko breathing technique

Ø  Herbal and traditional Chinese medicine

Ø  Homeopathy

Ø  Hypnosis and relaxation therapies


Other complementary or alternative approaches:

Ø  Manual therapy including massage and spinal manipulation

Ø  Physical exercise training

Ø  Family therapy 16



Since asthma involves inflammation and bronchoconstriction, treatment should be directed towards reducing inflammation and increasing bronchodilation. Restoration of normal airways function and prevention of severe acute attacks are the main goals of treatment. 8

The management of asthma stepwise approach based on the severity of the asthma it is shown in a figure 3. And choosing the device of inhaler in adults is based on the figure 4.



Clinically, corticosteroids decrease airway inflammation, decrease AHR, decrease mucus production and secretion, and improve the response to b2-agonists. Corticosteroids for the treatment of asthma are available in inhaled, oral, and inject able dosage forms.


Inhaled Corticosteroids:

In persistent asthma, inhaled corticosteroids provide the most comprehensive control of the inflammatory process and are the cornerstone of therapy. Inhaled corticosteroids are more effective than cromolyn, leukotriene modifiers, nedocromil, and theophylline in reducing markers of inflammation and AHR, improving lung function, and preventing emergency department visits and hospitalizations due to asthma exacerbations.

Systemic Corticosteroids:

Systemic corticosteroids are the cornerstone of the treatment of worsening asthma not responding to bronchodilators and acute severe asthma. For patients with worsening asthma not responding to bronchodilators, a short course or “burst” of systemic corticosteroids is effective for gaining control and preventing progression.


Beta2-Adrenergic Agonists:

Beta2-Agonists relax airway smooth muscle by directly stimulating beta 2-adrenergic receptors.18 They also increase mucociliary clearance and stabilize mast cell membranes. Inhalation, oral, and inject able dosage forms are available, and the inhalation dosage forms are most commonly used. Oral beta 2-agonists should not be used in acute asthma because of a delayed onset of action compared to the inhaled route. Inhaled beta 2-agonists are classified as either short- or long-acting based on their duration of action.


Short-Acting Inhaled Beta2-Agonists:

The most effective agents for reversing acute airway obstruction caused by bronchoconstriction and are the drugs of choice for treating acute severe asthma and symptoms of chronic asthma.


Long-Acting Inhaled Beta2-Agonists:

Are indicated for add on therapy for asthma not controlled on low to medium doses of inhaled corticosteroids. Adding a long-acting inhaled beta 2-agonist is at least as effective as doubling the dose of an inhaled corticosteroid with respect to improving lung function and symptom scores and decreasing nocturnal symptoms, reliever medication use, and asthma exacerbations.



Anticholinergic agents act by inhibiting the effects of acetylcholine on muscarinic receptors in the airways. They only protect against cholinergic-mediated bronchoconstriction and are not as effective as bronchodilators as are beta 2-agonists in asthma.


Leukotriene Modifiers:

Leukotriene modifiers either inhibit 5-lipoxygenase (zileuton) or competitively antagonize the effects of leukotriene D4 (montelukast and zafirlukast). These agents improve FEV1 and decrease asthma symptoms, rescue drug use, and exacerbations due to asthma. Although these agents offer the convenience of oral therapy for asthma, they are significantly less effective than low doses of inhaled corticosteroids.


Cromolyn and Nedocromil:

Are inhaled anti-inflammatory agents that block both the early- and late-phase response, Both agents are considered alternative therapies to inhaled corticosteroids for the treatment of mild persistent asthma: however, both are less effective than low doses of inhaled corticosteroids.



Figure 3: Asthma stepwise approach 16


Figure 4 : Choosing asthma inhaler devices for adults 17




Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma: however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use.18 It shows 3 different cellular actions-a) release of Ca2+ from sarcoplasmic reticulum, espesicially in skeletal and cardiac muscle. b) Inhibition of phosphodiesterase (PDE) which degrades cyclic nucleotides intracellularly and vasodilatation occur when cAMP levels rises in the concerned cells. c) Blockade of adenosine receptors: adenosine acts as a local mediator in CNS, CVS and other organs- contracts smooth muscles, especially bronchial: dilates cerebral blood vessels, depresses cardiac pacemaker and inhibits gastric secretion. Methylxanthines produce opposite effects.19



Omalizumab is a recombinant humanized monoclonal anti- IgE antibody that inhibits binding of IgE to receptors on mast cells and basophils, resulting in the inhibition of mediator release and attenuation of the early- and late-phase allergic response. It may be a treatment option for moderate to severe persistent asthmatics 12 years of age or older whose asthma is not controlled by inhaled corticosteroids and who have a positive skin test or in vitro reactivity to perennial allergens. Omalizumab significantly decreases inhaled corticosteroid use, number and length of exacerbations, and increases asthma-related quality of life.18



1.        Drezen JM.Asthma. In: Goldman L, Aausiello D, editors. Cecil Medicine. Philadelphia: Saunders Elsevier: 2008. p.

2.        Fauci AS, Kasper Dl, Longo DL, Braunwald E, Hauser SL, Jameson JL, Loscalzo J. Harrison’s preinciples of internal medicine. 17th ed. Philadelphia:  McGraw-Hill: 2008

3.        Viswanathan R, Prasad M, Thakur AK, Sinha SP, Prakash N, Mody RK, et al. Epidemiology of asthma in an urban population: a random morbidity survey. J Indian Med Assoc 1966: 46: 480-3

4.        Dahl R. Ciclesonide for the treatment of asthma. Therapeutics and clinical risk management. 2006: 2(1)25-37

5.        Kelly HW, Sorkness CA. Asthma. In: DIpiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, Pharmacotherpy A pathophysiologic approach. US: McGraw-hill,2009.7th ed,p. 463-95

6.        NHLBI, national asthma education and prevention program, expert panel report 2. Guidelines for the Diagnosis and Management of Asthma. NIH Publication no. 97-4051. Bethesda, MD, US department of health and human services, 1997

7.        Crompton GK, Haslett C, Chilvers ER. Disease due to respiratory system. Davidson’s, principles and practice of medicine. 19th ed: Elsevier: 2002

8.        Gibbs KP, Cripps D, Asthma: In. Walker R,Whittlesea, editors, Clinical Pharmacy  and Therapeutics. 4th ed. Philadelphia: Elsevier: 2008, p.367-85

9.        Blake K. Asthma. In: Herfindal ET, Gourley DR, editors. Text book of therapeutics. 7th ed. Philadelphia:Lippincott Williams and wilkins:2000,p.727-64

10.     Martin RJ. Asthma: In. Beers MH, Fletcher AJ, Jones TV, Porter R, Berkwits M, Kapalan JL, editors. The merck manual of medical information. 2nd ed. US: Merck: 2003, p.274-80.

11.     Guill MF, Asthma Update: Epidemiology and Pathophysiology. Pulmonology 2004: 25(9) 299-305.

12.     Firman P. Understanding asthma pathophysiology. Allergy Asthma Proc (0) 24: 79-83

13.     Making a difference in the management of asthma: A guide for respiratory therapists. NIH Publication no. 02-1964.US department of health services, 2003

14.     Global strategy for asthma management and prevention. Global Intiative for Asthma (GINA). Revised asthma guidelines 2007. Available at:

15.     British Guideline on the Management of Asthma A national clinical guideline. Revised June 2009.London. Available at:

16.     Asthma Management for children and adults. Colorado clinical guidelines. Available at: http://www.coloradoguidelines. org/pdf/guidelines/asthma/asthma magmt stepwise 4-29-08.pdf.

17.     Choosing asthma inhaler devices for adults. Respiratory system 2008. Available at: /formulary/sections/FF%20appendix%203A.pdf.

18.     Leader WG. Asthma. In: Burns MAC, Wells BG, Schwinghammer, Malone PM, Kolesar JM, Dipiro JT, Rotschafer JC, Pharmacotherapy principles and practice. : McGraw-hill, 2008.p. 209-30

19.     Tripathi KD. Essentials of Medical Pharmacology. 6th ed. New Delhi: JayPee: 2008.






Received on 02.03.2011          Modified on 08.03.2011

Accepted on 20.03.2011         © RJPT All right reserved

Research J. Pharm. and Tech. 4(6): June 2011; Page 883-890