Abstract

Chronic (long-term) asthma is a lung condition that narrows and inflames the airways. Chest tightness, shortness of breath, coughing, wheezing and whistling sounds made during breathing are symptoms of asthma. Coughing usually happens in the early hours of the morning or at night. People of all ages can have asthma, however, it typically first manifests in childhood. Edema of the mucosa of the airways, increased mucus secretion, injury to the airway epithelium, and/or smooth muscle spasms in the walls of smaller bronchi and bronchioles can all obstruct the airway. Nowadays, there are a plethora of commercially accessible treatments to treat asthma. However, to fully recover from this illness, patients must avoid antigen exposure, reduce hyperactivity and inflammation in their bronchi, and utilize medication to widen their limited airways. Allergens (pet dander, pollen), respiratory illnesses, physical exercise, air pollution, tobacco, some medications, and exposure to irritants like chemicals or solid odours are common causes of asthma attacks. More than 80 per cent of deaths from asthma happen in low- and lower-middle-income nations. According to estimates from the World Health Organization (WHO), 300 million individuals globally are estimated to have asthma. We address the pathophysiology, epidemiology, and aetiology of asthma in this review paper.

Keywords

Introduction

The hallmark of asthma is a persistent inflammation of the airways with an excess of mast cells, activated T helper lymphocytes, and eosinophils. The mediators released by these inflammatory cells cause remodelling, mucus secretion, and bronchoconstriction. Asthma causes histopathological alterations in the bronchial and bronchiolar walls that affect the mucosa (including the lamina propria and epithelium), submucosa (which includes mucus-secreting glands and airway smooth muscle (ASM)), and adventitia (the interface between airway and surrounding lung parenchyma) (1,2). Commonly occurring, asthma can range in intensity from a very mild, sporadic wheeze to an abrupt, potentially fatal airway closure. It typically manifests in childhood and is linked to other atopy symptoms including hay fever and eczema. A common childhood ailment that causes repeated hospital hospitalizations and higher healthcare expenses is asthma. The main characteristic is airway hyperresponsiveness, which has various causes. In the absence of early treatment, asthma has a significant death rate(3–6). An ongoing inflammatory condition of the airways is called asthma. The chronic inflammation is linked to airway hyperresponsiveness, which causes recurrent symptoms including coughing, dyspnea (shortness of breath), wheezing, and chest tightness in response to triggers like exercise and allergens. A common but fluctuating blockage of airflow in the lungs during symptom episodes is usually reversible, either on its own or with the right asthma medication (7). Patients experiencing frequent coughing, wheezing, tightness in the chest, and dyspnea may have asthma. Strong indications of asthma include varying symptoms, worsening at night, happening after exposure to allergens or irritants, and responding well to asthma medication (8). Other conditions such as chronic obstructive pulmonary disease (COPD), bronchitis, chronic sinusitis, gastroesophageal reflux disease, recurrent respiratory infections, and heart disease should be ruled out as potential causes of the symptoms of suspected asthma.  Patients with asthma may also be identified by a positive family history of asthma or other atopic diseases, as well as by a personal history of atopic disorders, especially allergic rhinitis. Examining the patient's history for potential asthma triggers, such as cockroaches, dust mites, animal dander, molds, pollens, exercise, and exposure to cold air or tobacco smoke, is also crucial. Inhaling substances that are encountered at work may potentially result in asthma (9). A serious global health issue, ASTHMA is becoming more and more common in many nations. Over 80% of asthma deaths occur in low- and lower-middle-income countries. The World Health Organization (WHO) estimates that 300 million people worldwide suffer from asthma, and that 255,000 of those deaths occurred in 2005. Asthma prevalence in India had previously been estimated to be around 3% (30 million people), with 2.4% of individuals over the age of 15 and between 4% and 20% of children affected. Asthma was predicted to be the cause of 57,000 fatalities in India in 2004.5 It is one of the main causes of morbidity and mortality in rural areas of the country and is expected to become more common in the upcoming decades. With data from 109041 households and covered regions representing over 99% of India's population, the third National Family Health Survey (NFHS-3, 2005–2006) offers a rare opportunity to examine the prevalence of asthma and its societal, environmental, lifestyle, and dietary determinants (10).

EPIDEMIOLOGY

Asthma is a prevalent illness that affects 2% to 4% of persons in less developed nations and 15% to 20% of people in industrialized nations. Children are notably more likely to experience it. Regardless of lung function testing, up to 40% of children will experience a wheeze at some point. If this wheeze is reversible with beta-2 agonists, it is referred to as asthma. Since asthma is linked to inhaled particles and tobacco smoke, it is more prevalent in populations where these environmental exposures occur. When a boy to girl ratio is 2:1 during childhood, asthma is more common in boys until puberty, at which point the ratio drops to 1:1. Females are more likely than males to get asthma after puberty, and after the age of forty, most adult-onset cases occur in adults. Because of decreased lung function and airway reactivity, asthma is more common in older people. Approximately 66% of asthma cases are diagnosed prior to the age of 18. Nearly half of children with asthma have a reduction in severity or complete cessation of symptoms in their early adult years (11–14).

ETIOLOGY

Asthma manifests itself in a multitude of diverse phenotypes and encompasses a spectrum of disorders. Genetic predisposition, specifically a personal or family history of atopy (propensity to allergy, commonly visible as eczema, hay fever, and asthma), is one of the recognized factors related with asthma (15,16).There are several diverse phenotypes associated with asthma, each with its own genesis, presentation, and pathophysiology. The identified phenotypes of asthma are associated with various risk factors, namely genetic, environmental, and host variables. Despite being widespread, a family history of asthma does not guarantee the development of asthma. The idea that environmental changes are a major contributing factor to the current asthma epidemic is supported by the notable increases in the incidence of asthma over the previous few decades as well as the geographic variance in base prevalence rates and the size of the increases.

Furthermore, the relevant risk factors for asthma may vary over time, and environmental triggers may impact a person differently depending on when in their life they experience them. Studies evaluating risk variables over a short period of time may indicate a decreased chance of asthma, but longer-term follow-up may link the same factors to an increased risk. This pattern might be related to the overlap of several early-life wheeze phenotypes, only some of which continue into later childhood and adulthood as asthma. This phenomenon prompts us to look at the risk factors for asthma that persist at various ages, particularly during pregnancy, early childhood, teenage years, and, in a nutshell, adulthood (17,18). Exposure to tobacco smoke and other inflammatory gasses or particulate matter is also linked to asthma. It is generally agreed that asthma is a multifactorial pathology influenced by both genetics and environmental exposure, but the overall etiology is complex and still not fully understood, particularly when it comes to predicting which children with pediatric asthma will go on to have asthma as adults (up to 40% of children have a wheeze, 1% of adults have asthma). Asthma triggers include: Chronic sinusitis, exercise, gastric reflux illness, viral respiratory tract infections, Allergens in the environment Using beta-blockers and aspirin smoke from tobacco, insects, vegetation, overweight,

stress or emotional variables (19).

PATHOPHYSIOLOGY

An environmental trigger is frequently the cause of asthma, which is an acute, completely reversible inflammation of the airways. An irritant (such as cold air) or allergen (such as pollen) is inhaled to start the pathological process. This causes bronchial hypersensitivity, which in turn causes inflammation of the airways and an increase in mucus production. The result is a marked increase in airway resistance, which is especially noticeable during expiration (19). T helper cell type-2 (Th2) immunological responses, which are common to other atopic diseases, are linked to asthma. Chronic airway inflammation is caused by a variety of allergic (such as dust mites, cockroach remains, furred animals, molds, pollens) and non-allergic (such as infections, tobacco smoking, cold air, exercise) stimuli that set off a chain reaction of immune-mediated processes. Certain cytokines, including as interleukin (IL)-4, IL-5, IL-9, and IL-13, are released by elevated Th2 cell counts in the airways and encourage eosinophilic inflammation and mast cell production of immunoglobulin E (IgE). When IgE is produced, inflammatory mediators like histamine and cysteinyl leukotrienes are released. These mediators cause swelling, bronchospasm (contraction of the smooth muscle in the airways), and increased mucous secretion (mucous hypersecretion), all of which are asthma symptoms (7,20). In response to an instigating allergen, mediators and cytokines generated in the early phase of the immune response set off a second inflammatory reaction known as the late-phase asthmatic response, which exacerbates airway inflammation and bronchial hyperreactivity. There is evidence to show that asthma may have a hereditary predisposition to develop. Numerous chromosomal areas, including those connected to the synthesis of inflammatory mediators, the expression of airway hyperresponsiveness, and the generation of IgE antibodies, have been linked to an increased risk of developing asthma. To identify the precise genes linked to asthma and the gene-environment interactions that can result in the disease's manifestation, more research is necessary (9). The following factors combine to cause airway obstruction: Infiltration of inflammatory cells. hypersecretion of mucus coupled with the development of mucus plugs. smooth contraction of the muscles. The thickening of the basement membrane, collagen deposition, and desquamation of the epithelium may cause these irreversible alterations to become irreversible over time. In chronic diseases characterized by smooth muscle hypertrophy and hyperplasia, airway remodeling takes place. Treatment for asthma may become more challenging if it is not addressed quickly because mucus production blocks inhaled medication from reaching the mucosa. Additionally, inflammation gets more edematous. In theory, complete resolution is necessary for asthma; however, in practice, this is not verified or tested. Beta-2 agonists, such as salbutamol, salmeterol, and albuterol, resolve this process, and muscarinic receptor antagonists, such as ipratropium bromide, can also help. These agents function by lowering inflammation and relaxing the bronchial musculature, which lowers mucus production (21).

DIAGNOSIS

Laboratory: If the patient gets a large dose of salbutamol or repeats the medication, urea and electrolytes (kidney function) should be taken since one of the adverse effects of salbutamol is the temporary shifting of potassium into the intracellular space, which can result in a brief, iatrogenic hypokalaemia. While widespread, eosinophilia is not asthma-specific. Sputum eosinophil counts have been shown in recent research to potentially direct therapy. Furthermore, a serum IgE increase may be present in certain cases. Respiratory acidosis and hypoxemia may be shown by arterial blood gas analysis. Although periostin may be a marker for asthma, its clinical significance is still unknown, according to studies (19). An ECG will show sinus tachycardia, which could be caused by theophylline, albuterol, or asthma. Special Tests: The best diagnostic technique is spirometry, which reveals an obstructive pattern that salbutamol can either totally or partially relieve. To ascertain the severity of the disease, spirometry should be performed prior to starting treatment. Treatment can reverse airway blockage, which is shown by a lower ratio of FEV1 to FVC. The patient is given short-acting beta 2 agonists by inhalation to test for reversibility, and then the spirometry test is repeated. A 12% or 200ml increase in FEV1 over the baseline indicates reversibility and is diagnostic for bronchial asthma. Peak expiratory flow monitoring is widely used nowadays and makes therapeutic response tracking possible. The fact that this test depends on effort is one of its limitations. Bedside: Pulse oximetry can be helpful in monitoring for worsening conditions or determining how severe an asthma attack is. Be aware that a dropping pO2 on pulse oximetry is a late discovery, indicating a severely ill or peri-arrest patient. This is due to pulse oximetry latency and the physiological reserve of many patients. Peak flow measurements are useful for evaluating asthma as well, and they should always be compared to a nomogram and the patient's typical baseline function. Peak flow, expressed as a percentage of predicted peak flow, is measured in relation to the various severity of acute asthma attacks (19). Imaging: A chest x-ray is a crucial diagnostic, particularly for individuals who have a medical history that puts them at risk for an infection or foreign substance. Patients who have repeated symptoms and don't improve with treatment are given a CT scan of their chest.

HANDLING THE CONDITION OF ASTHMA

The main objective of managing asthma is to bring the condition under control and keep it there in order to lower the risk of morbidity and death and avoid asthma exacerbations, which are defined as sudden and/or progressive worsening of asthma symptoms that frequently call for immediate medical attention and/or the use of oral steroid therapy. drug for relieving acute symptoms: All asthma patients should be provided inhaled rapid-acting beta2-agonists, as they are the best drug for this purpose. For this purpose, some Long-acting beta-agonists (LABAs) (formoterol) and several short-acting beta2-agonists (SABAs) (salbutamol, terbutaline, etc.) are authorized in Canada. SABAs should only be used when necessary to treat symptoms. A weakening of control and the need to reevaluate treatment to bring symptoms under control are indicated by increased use, defined as three or more times per week. Formoterol, in contrast to other LABAs, acts quickly, making it useful for treating acute symptoms. However, formoterol should only be used as a reliever in patients 12 years of age or older who are on regular controller therapy with an ICS, as LABA monotherapy has been linked to an increased risk of asthma-related morbidity and death (8,22). Conservative Measures: The patient should be cooled, moved outside or away from the allergen's likely source, and soothed to help them relax. Sometimes people remove their clothes and wash their mouths and faces to get rid of allergies, however this practice is not supported by research. Controlling the environment is essential to preventing recurring episodes. Avoiding allergens can greatly enhance one's quality of life. Tobacco, dust mites, animals, and pollen must all be avoided. In obese asthmatics, losing weight improves control. Immunotherapy using allergens is still debatable. Extensive research has not yielded any noteworthy advantages, and the method is excessively costly. Patients with a positive skin test result who have moderate to severe asthma should consider monoclonal antibody therapy. The medication may reduce IgE levels, which will lessen the synthesis of histamine. The injections are expensive, though. A relatively recent procedure called bronchial thermoplasty improves airway constriction by applying heat energy to the airway wall. Numerous studies shown that it can lower the number of emergency room visits and school absences (23–25). Medical therapy consists of anti-inflammatories such as inhaled steroids (typically beclometasone, but steroids via any route will be useful) and bronchodilators such as beta-2 agonists and muscarinic antagonists (salbutamol and ipratropium bromide, respectively). The therapy of chronic asthma involves five steps: treatment is initiated based on the severity of the condition and is then modified or recommenced based on the patient's response. 1. Low dose inhaled corticosteroids and formoterol are the preferred controllers. 2: Daily low dosage inhaled corticosteroids combined with on-demand short-acting beta 2 agonists are the recommended controls. 3. Long-acting beta 2 agonists and low-dose inhaled corticosteroids, together with as-needed short-acting beta 2 agonists, are the recommended controls. 4. A medium-dose inhaled corticosteroid, a long-acting beta 2 agonist, and short-acting beta 2 agonists as needed make up the recommended controller. 5. Inhaled corticosteroid at a high dosage, long-acting beta 2 agonist, long-acting muscarinic antagonist, and anti-IgE. Signs that warrant admission: When deciding whether to admit a patient who has not responded to three inhaled bronchodilator doses, the following criteria should be considered: The degree of airflow blockage, length of time that asthma has been present, Reaction to drugs, Sufficient assistance at home, Any kind of mental disease The management of patients with severe asthma involves the use of high flow oxygen inhalation, systemic steroids, short-acting beta 2 agonists, short-acting muscarinic antagonists, back-to-back nebulizations, and intravenous magnesium sulfate. Reducing mortality is aided by early intensive care team consultation. Mechanical ventilation and early intubation are necessary in cases of asthma that are close to fatality (19,26).

DISCUSSION AND CONCLUSION

An overview of asthma, its several causes, epidemiology, pathophysiology, and alternate therapies is provided at the outset of our review articles. Our data shows that pharmaceuticals does treat, but not completely, while natural and non-pharmacological supplements have no side effects and deliver a respectable result over time. More randomized controlled studies are required in the area of asthma treatment. We would like to carry out an initial investigation on asthma in the future. Future counseling-based research in our nation or state will evaluate patients' physical and mental health and generate more precise data on asthma and its treatment, thanks to the assistance of our colleagues.

ETHICAL STATEMENT

A pharmacist works to advance each patient's well-being in a discreet, kind, and caring way.

ACKNOWLEDGEMENT

Authors would like to thank, Azad Institute of Pharmacy & Research, Lucknow, U.P, India, Lucknow, Uttar Pradesh, India for extending their facilities.

CONFLICT OF INTEREST

The authors attest that they are free of any known financial or personal conflicts of interest that would taint the findings of this study.

INFORMED CONSENT       

Using websites, review articles, and other sources to produce research content.

REFERENCE

1. Illinois M. Allergic Reactibility. 1913;30.
2. Hogg JC. The pathology of asthma. Clin Chest Med. 1984;5(4):567–71.
3. Scirica C V., Celedón JC. Genetics of asthma potential implications for reducing asthma disparities. Chest. 2007;132(5 SUPPL.):770S-781S.
4. Teras LR. HHS Public Access. Physiol Behav [Internet]. 2017;176(10):139–48. Available from: file:///C:/Users/Carla Carolina/Desktop/Artigos para acrescentar na qualificação/The impact of birth weight on cardiovascular disease risk in
5. Tesfaye ZT, Gebreselase NT, Horsa BA. Appropriateness of chronic asthma management and medication adherence in patients visiting ambulatory clinic of Gondar University Hospital: A cross-sectional study. World Allergy Organ J. 2018;11(1):1–7.
6. Lee J, McDonald C. Review: Immunotherapy improves some symptoms and reduces long-term medication use in mild to moderate asthma. Ann Intern Med. 2018;169(4):JC17.
7. Hozawa S, Haruta Y, Terada M, Yamakido M. Effects of the addition of beta2-agonist tulobuterol patches to inhaled corticosteroid in patients with asthma. Allergol Int [Internet]. 2009;58(4):509–18. Available from: http://dx.doi.org/10.2332/allergolint.08-OA-0060
8. Kaplan AG, Balter MS, Bell AD, Kim H, McIvor RA. Diagnosis of asthma in adults. C Can Med Assoc J. 2009;181(10):210–20.
9. Kim H, Mazza J. IMMUNOLOGY. 2014;(May).
10. Agrawal S, Pearce N, Ebrahim S. Prevalence and risk factors for self-reported asthma in an adult Indian population: A cross-sectional survey. Int J Tuberc Lung Dis. 2013;17(2):275–82.
11. Burrows B, Barbee RA, Cline MG, Knudson RJ, Lebowitz MD. Characteristics of asthma among elderly adults in a sample of the general population. Chest [Internet]. 1991;100(4):935–42. Available from: http://dx.doi.org/10.1378/chest.100.4.935
12. D’Amato M, Molino A, Calabrese G, Cecchi L, Annesi-Maesano I, D’Amato G. The impact of cold on the respiratory tract and its consequences to respiratory health. Clin Transl Allergy [Internet]. 2018;8(1):1–8. Available from: https://doi.org/10.1186/s13601-018-0208-9
13. Haley WE, Freeman. ?????? HHS Public Access. Physiol Behav. 2018;176(1):139–48.
14. Fahy J. American Thoracic Society Proceedings of the ATS Workshop on Refractory Asthma. Am J Respir Crit Care Med. 2000;162(10):2341–51.
15. Aggarwal B, Mulgirigama A, Berend N. Exercise-induced bronchoconstriction: prevalence, pathophysiology, patient impact, diagnosis and management. npj Prim Care Respir Med [Internet]. 2018;28(1). Available from: http://dx.doi.org/10.1038/s41533-018-0098-2
16. Piloni D, Tirelli C, Domenica R Di, Conio V, Grosso A, Ronzoni V, et al. Asthma-like symptoms: Is it always a pulmonary issue? Multidiscip Respir Med. 2018;13(1):4–6.
17. Subbarao P, Mandhane PJ, Sears MR. Asthma: Epidemiology, etiology and risk factors. C Can Med Assoc J. 2009;181(9).
18. Burke W, Fesinmeyer M, Reed K, Hampson L, Carlsten C. Family history as a predictor of asthma risk. Am J Prev Med. 2003;24(2):160–9.
19. Hashmi MF, Tariq M, Cataletto ME. Asthma. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan- . Available from: https://www.ncbi.nlm.nih.gov/books/NBK430901/. 2024;430901.
20. Lemanske RF, Busse WW. Asthma: Clinical expression and molecular mechanisms. J Allergy Clin Immunol [Internet]. 2010;125(2 SUPPL. 2):S95–102. Available from: http://dx.doi.org/10.1016/j.jaci.2009.10.047
21. Southworth T, Kaur M, Hodgson L, Facchinetti F, Villetti G, Civelli M, et al. Anti-inflammatory effects of the phosphodiesterase type 4 inhibitor CHF6001 on bronchoalveolar lavage lymphocytes from asthma patients. Cytokine [Internet]. 2019;113(November 2017):68–73. Available from: https://doi.org/10.1016/j.cyto.2018.06.007
22. Fitzgerald JM, Leigh R, Licskai C, Rowe BH, Bowie D. Concensus summary for Asthma in children aged six years of age and over , and adults. Can J Respirol. 2010;17(1):15–24.
23. Jilani TN, Preuss CV, Sharma S. Theophylline. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan- . Available from: https://www.ncbi.nlm.nih.gov/books/NBK519024/. 2024;519024.
24. Almadhoun K, Sharma S. Bronchodilators. [Updated 2023 Apr 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519028/. 2024;519028.
25. Gosens R, Gross N. The mode of action of anticholinergics in asthma. Eur Respir J [Internet]. 2018;52(4). Available from: http://dx.doi.org/10.1183/13993003.01247-2017
26. Sheetu Singh, Neeraj Sharma, Udaiveer Singh, Tejraj Singh, Mangal DK, Singh V. Nasopharyngeal wash in preventing and treating upper respiratory tract infections: Could it prevent COVID?19? Lung India [Internet]. 2018;35(1):41–6. Available from: https://pubmed.ncbi.nlm.nih.gov/32367