Asthma

ASTHMA
COLLEGE : SMT.KISHORITAI BHOYAR COLLEGE OF PHARMACY, KAMPTEE , NAGPUR.

1. ASTHMA KSHITIJ B.MANKAR M.PHARM 1 ST YEAR GUIDED BY : MANISH AGLAWE SIR

2. DEFINITION : Asthma is a chronic heterogeneous disease of the lower airways characterized by chronic inflammation and airway hyper-reactivity leading to cough, wheeze, difficulty in breathing, and chest tight- ness . It is usually characterized by chronic airway inflammation, bronchial reversible obstruction and hyperresponsiveness to direct or indirect stimuli.

3. ETIOLOGY :

4. CAUSES : Asthma triggers Exposure to various irritants and substances that trigger allergies (allergens) can trigger signs and symptoms of asthma. Asthma triggers are different from person to person and can include: Airborne allergens, such as pollen, dust mites, mold spores, pet dander or particles of cockroach waste Respiratory infections, such as the common cold Physical activity Cold air Air pollutants and irritants, such as smoke

5. Certain medications, including beta blockers, aspirin, and nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve) Strong emotions and stress and preservatives added to some types of foods and beverages, including shrimp, dried fruit, processed potatoes, beer and wine Gastroesophageal reflux disease (GERD), a condition in which stomach acids back up into your throat

6. RISK FACTOR : Family history Viral respiratory infections Allergies Occupational exposures Smoking Air Pollution Obesity

7. Having a blood relative with asthma, such as a parent or sibling Having another allergic condition, such as atopic dermatitis — which causes red, itchy skin — or hay fever — which causes a runny nose, congestion and itchy eyes Being overweight Being a smoker Exposure to secondhand smoke Exposure to exhaust fumes or other types of pollution Exposure to occupational triggers, such as chemicals used in farming, hairdressing and manufacturing

8. SYMPTOMS : Severe wheezing both in and out Coughing that won't stop Very rapid breathing Chest pain or pressure Tightened neck and chest muscles, called retractions Difficulty talking Feelings of anxiety or panic Pale, sweaty face Blue lips or fingernails

9. Types of Asthma: Allergic Asthma ( extrinic asthma) Non-Allergic Asthma ( intrinsic asthma) Mixed Asthma Cough-Variant Asthma (very common in children) Exercise Induced Asthma Noctornal Asthma Occupational Asthma

10. Allergic Asthma: When the symptoms are induced by a hyperimmune response to the inhalation of specific allergens. Type –I (IMMEDIATE ) hypersensitivity reaction is the basis of the IgE . When person come across an allergy trigger, our body makes molecules called IgE antibodies. These trigger a series of reaction that cause swelling , runny nose and sneezing. Extrinsic asthma symptoms occur in response to allergens, such as dust mites, pollen, and mold. It is also called allergic asthma and is the most common form of asthma.

11. Symptoms of Allergic Asthma: The symptoms of allergic asthma are generally the same as those of non-allergic asthma. They include: Coughing Wheezing Shortness of breath Fast breathing Tightening of the chest

12. B. Non –Allergic Asthma: This type of asthma is triggered by the presence of irritants in the air that are not related to allergies. This irritants stimulate parasympathetic nerve fibers in the airways causing broncho -constriction and inflammation. Non-allergic asthma is triggered by factors other than allergens. These can include : Viral respiratory infections Exercise Irritants in the air Stress Drugs and certain food additives Weather conditions

13. Symptoms of Non-allergic asthma: The most common signs of asthma are: Coughing, especially at night, during exercise or when laughing Difficulty breathing Tightness in the chest Shortness of breath Wheezing Intrinsic asthma has a range of triggers, including weather conditions, exercise, infections, and stress.

14. C. Mixed Asthma: Mixed asthma is the combination of both allergic and non-allergic asthma. This is the most common form of asthma.

15. d. COUGH –VARIANT ASTHMA: Cough variant asthma  is a type of  asthma  that features a dry, non productive  cough . There may be no traditional  asthma  symptoms, such as wheezing or shortness of breath. An ongoing  cough  is often the only symptom.  Cough variant asthma  (CVA) is a common  asthma  variation in children.

16. E. EXERCISE INDUCE ASTHMA:   Exercise-induced asthma is asthma that is triggered by vigorous or prolonged exercise or physical exertion. Most people with chronic asthma experience symptoms of asthma during exercise. EIB is caused by the loss of heat, water or both from the airways during exercise when quickly breathing in air that is drier than what is already in the body . 

17. F. OCCUPATIONAL ASTHMA: People with this condition usually work around chemical fumes, dust or other irritants in the air. If you’ve been diagnosed with asthma that has another cause, it can be worsened by airborne irritants at work. Triggers may include chemicals used in manufacturing; paints; cleaning products; dusts from wood, grain and flour; latex gloves; certain molds; animals; and insects.

18. RISK FACTOR OF OCCUPATIONAL ASTHMA: Bakers Detergent manufacturers Drug manufacturers Farmers Grain elevator workers Laboratory workers (especially those working with laboratory animals) Metal workers Millers Plastics workers Woodworkers

19. PATHOPHYSIOLOGY:

20. Asthma is associated with T-helper cell type-2 (Th-2) immune responses. Its may include allergic and non-allergic stimuli. which produces a cascade of events leading to chronic-airway inflammation. Elevated levels of Th-2 cells in airways releases specific cytokines including IL-4,IL-5,IL-9 and IL-13 and promote eosinophilic inflammation and immunoglobulin E ( IgE ) production. IgE production , in turns , triggers releate of inflammatory mediators,

21. such as histamine and cysteinyl leukotrienes , that cause bronchospasm (contraction of the smooth muscle in the airways), edema, and increased mucous secretion, which lead to the characteristic symptoms of asthma.

22. IL-4, IL-13, and IL-5 are key drivers of type 2 inflammation IL-4 and IL-13 are central Type 2 cytokines with distinct and overlapping roles : IL-4 drives Th2 cell differentiation and mediates the production of downstream Type 2 cytokines IL-13 mediates goblet cell hyperplasia and increased mucus secretion , and promotes airway obstruction , bronchial hyperactivity, smooth muscle hypertrophy , and airway remodelling . IL-4 and IL-13 play an important role in class switching of B cells to produce IgE . IL-5 mediates the differentiation of eosinophils in bone marrow; IL-4 and IL-13 drive the tracking of eosinophils to sites of inflammation.

23. PATHOPHYSIOLOGY: TYPE 2 ASTHMA

24. IL-4 drives Th2 cell differentiation IL-4 and IL-13 promote class switching of B cells to produce IgE . ALLERGIC- ASTHMA

25. DIAGNOSIS: Patient history Physical Examination Chest X-ray Pulmonary Function Test Blood and Sputum Test Allergy Prick skin Test Spirometry Test FEV ( Force Expiratory Volume) FVC ( Force Vital Capacity)

26. DIFFERENTIAL DIAGNOSES OF ASTHMA:

27. Asthma diagnosis algorithm

28. DRUGS FOR ASTHMA:

29. 1.BRONCHODILATORS: Beta-2 agonists: Beta-2 agonists are bronchodilators that play an important role in asthma control and treatment of acute exacerbations. They bind to the beta-2 adrenergic receptors on the bronchial smooth muscle cells, causing smooth muscle relaxation and bronchodilation . Increased levels of energy –producing cAMP . This is done by competitively inhibiting phosphodiesterase (PDE) ,the enzyme, that breaks the cAMP . Its result into decreased cAMP levels, cause SM relaxation,bronchodialation and increased air flow.

30. LEUKOTRIENE ANTAGONISTS: Leukotrienes are lipid mediators involved in bronchoconstriction and airway inflammation. Leukotriene -modifying drugs, including zafirlukast , montelukast , and zileuton , work by inhibiting leukotriene synthesis or as competitive antagonists of the leukotriene receptors. Cysteinyl leukotrienes are released from mast cells and eosinophils and are involved in bronchial smooth muscle contraction and increased mucus secretion. By working as receptor antagonists and inhibiting leukotriene synthesis, these drugs downregulate airway inflammation; they have also been shown to improve asthma symptoms and lung function and serve as an add-on therapy to ICS. Current guidelines recommend the use of leukotriene receptor antagonists only as an alternative treatment to ICS in those with moderate persistent asthma who cannot tolerate ICS and as an add-on therapy to those receiving combined LABA/ICS.

31. MAST CELL STABILIZERS: Its inhibits degranulation of mast cells. Release of mediators like histamines,LT,PAF,IL is inhibited. This action may include delayed Cl channel. Chemotaxis of inflammatory cells is inhibited. Bronchial hyperactivity of histamine is reduced. Bronchospam due to various stimuli is prevented. It can’t be used to prevent attack of asthma because it does not affect the constrictor action.

32. COTICOSTEROIDS: Corticosteroids are not bronchodialators . It is given as prophylactic medications,use alone or combined with beta-agonists. Inhibition of phospholipase A2 , decreased prostaglandin and leukotrienes . Mast cell stabilization ,decreased histamine release. Upregulation of beta2 receptors.

33. ANTI- IgE ANTIBODY: The drug omalizumab is actually a humanized monoclonal antibody. It is administered I.M or S.C. It neutralizes free IgE in circulation without activating mast cellls and other inflammatory cells. So IgE level in plasma is down and so,mast cell- IgE mediated histamine release is inhibited. cause bronchoconstriction

34. Asthma comorbidities and stroke: Chronic respiratory diseases are associated with a number of comorbidities due to their pro inflammatory state. Asthma is not an exception and there list of commonly encountered comorbidities includes chronic rhinitis, chronic sinusitis/rhino-sinusitis, gastro-esophageal reflux disease, obstructive sleep apnea/sleep-disordered breathing, psychological disturbances (particularly depression and anxiety disorders), chronic/recurrent respiratory infections, hyperventilation syndrome, hormonal disturbances and other . There are also possible emerging comorbid conditions such as cardiovascular, obesity, metabolic syndrome, diabetes mellitus, degenerative joint disease/arthritis and psychiatric diseases. Some of these comorbidities lead to an increased risk of stroke and are highly prevalent in asthma patient. This raises the question that the increased risk of stroke in asthma patients may be due to confounding effect. Nevertheless, the important point is that proper screening and diagnosis of comorbidities in asthmatics is essential for preventing serious complications including stroke.

35. Bronchial Thermoplasty : Bronchial thermoplasty (BT) offers a nonpharmacologic therapy for those with asthma unresponsive to standard treatment with ICS and bronchodilators. Bronchial thermoplasty  is a treatment for severe asthma approved by the FDA in 2010 involving the delivery of controlled, therapeutic radiofrequency energy to the airway wall, thus heating the tissue and reducing the amount of smooth muscle present in the airway wall. BT uses thermal energy to bronchoscopically ablate airway smooth muscles to decrease bronchoconstriction and airway hyperplasia. The effectiveness of this treatment was initially seen in the AIR (ASTHMA INTERVENTION RESEARCH) trial in 2007, which randomised patients with moderate or severe asthma to BT or a control group.

36. Those who received BT had significant improvements in morning PEFR, percentage of symptom-free days, and symptom score reduction. In addition, the RISA( Research in severe Asthma) trial randomised 32 poorly controlled asthma patients to BT or a control group and reported that the BT group had increased initial short-term morbidity but significantly improved pre-bronchodilator FEV1 and asthma symptom score. These studies were followed by the AIR2 trial, which again demonstrated significant improvements in asthma symptoms and exacerbations in those randomised to BT. BT may therefore be an effective non-pharmacologic treatment for asthma in those with severe disease resistant to pharmacotherapy; however, there are significant adverse reactions associated with BT, including life-threatening severe exacerbations and death.

37. Summary and future perspective: It is important to clarify whether asthma increase the risk of all stroke types and to elaborate safe and effective methods for stroke prevention. More studies are required to evaluate whether, adjusting the therapy with anticoagulants is a correct strategy, as well as, which predictors are the best to be implemented in routine monitoring of asthma patients. In general, the interaction between lungs and the brain is complex. The pro-inflammatory state generated at the level of the lungs leads to atherosclerosis, comorbid conditions, pro coagulatory state. SCS therapy decreases the inflammatory process but in turn , also leads to cardiovascular and metabolic diseases.

38. Al-though, ICS are safer, they are also linked to comorbidities . SABA and LABA are directly linked to arrhythmogenic effect, which in turn can lead to thrombo embolism. It seems that all of the above mentioned main drug groups that are used for asthma treatment are to some to stroke. Antimuscarinic agents on the other did not demonstrate this effect. Similarly, there are other emerging drug groups which may demonstrate a better safety profile regarding cardiovascular and metabolic co-morbidities as well as stroke risk. We also need agents that can effectively combat and limit the inflammatory state at the level of the lungs. Asthma-related comorbidities should be at special attention in lights of the fact that the majority are linked to cerebro vascular disease.

39. The findings of vitamin D implications in asthma evolution and stroke outcomes should be confirmed in a prospective fashion that involves the generation of an efficient multivariate model, in order to include vitamin D supplementation as an adjuvant therapy for asthma patients, especially those with increased riskfor stroke. Furthermore, current treatment options are limited and may not be effective for all patient populations. Hence, new treatment options with superior efficacies to treat these diseases are urgently required as potential substitution, alternative or adjunct therapy to currently available therapies.

40. REFERNECES: Advances and recent developments in asthma in 2020 © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. http://www.wileyonlinelibrary.com/journal/all Bronchial asthma - Issues for the developing world Indian Journal of Medical Research Asthma: Diagnosis and Treatment *Jennifer Y. So, Albert J. Mamary , Kartik Shenoy Division of Thoracic Medicine and Surgery, Temple University Hospital, Philadelphia, Pennsylvania, USA

41. Asthma and stroke: a narrative review Corlateanuet al. Asthma Research and Practice (2021) 7:3 https://doi.org/10.1186/s40733-021-00069-x Computer-Aided Intelligent System for Diagnosing Pediatric Asthma ArticleinJournal of Medical Systems · July 2010 https://www.knowtype2asthma.com/science-cytokines Wenzel SE. Emergence of biomolecular pathways to define novel asthma phenotypes: type-2 immunity and beyond. Am J Respir Cell Mol Biol. 2016;55(1):1-4. https://acaai.org/asthma/asthma-treatment KD.TRIPATI 8 TH EDITION