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  • MS Slide 2 Asthma is a chronic inflammatory disease of the airways. 1 Chronically inflamed airways become hyperresponsive to a variety of stimuli and obstructed by bronchoconstriction, edema, excess mucus production, and infiltrating inflammatory cells. 1,2 The resulting airflow limitation leads to the characteristic symptoms of asthma: recurrent episodes of wheezing, breathlessness, chest tightness, and cough. 2 Chronic, active inflammation is present and central to the disease in all patients with asthma, even when no symptoms are evident. 2 Therefore, the goal of asthma treatment is to suppress airway inflammation and thereby modify disease progression. 2 Accordingly, guidelines issued by the Global Initiative for Asthma (GINA) recommend the use of anti-inflammatory agents early in the disease. 1 Ref 1, p 4, ¶4, L1   Ref 1, p 4, ¶4, L1-5   Ref 2, p 704, C2, L3-9   Ref 2, p 704, C1, ¶7, L1-6 Ref 2, p 704, C1, ¶8, L1-2 C2, L1-3   Ref 2, p 704, C2, ¶1, L4-8   Ref 1, p 15, Table p 17, Table
  • MS Ref 3, p 10 C1 ¶1, L1-8 Ref 4, p S1 C1, ¶1, L 1-11 Ref 4, p S2, C2, ¶2, L12-17   Ref 5, p S31, C2, ¶2, L1-4   Ref 6, p 108, C2, ¶1, L6-10; p 112, C2, ¶1, L1-4 Ref 7, p S38 C2, ¶1, L11-14 Ref 8, p 1175, C2, ¶2,3 Slide 4 It is well established that asthma is a disease of airway inflammation, 3 which if uncontrolled causes asthma symptoms such as airway hyper-responsiveness and bronchoconstriction. This pictogram serves to illustrate dual pathways of asthmatic inflammation composed of both the cysteinyl leukotriene-mediated pathway and that which is sensitive to steroids. Leukotrienes have been shown to be an important mediator of inflammation in early asthma and throughout all stages of disease. Therefore, the leukotriene pathway represents a viable therapeutic target. 4 An accumulating body of evidence suggests that persistent asthmatic inflammation is paralleled by airway remodeling, even in early asthma. 4 Cysteinyl leukotrienes (CysLTs) are important drivers of the inflammation process. 5 Preclinical studies in mice have shown that remodeling in chronic asthma also eventually involves corticosteroid-sensitive mediators such as cytokines (e.g., interleukin [IL]-4, IL-5, IL-13). 6-8
  • MS Slide 6 A recent immunohistochemical study identified the CysLT 1 receptor protein in smooth-muscle cells of the normal human lung and normal human peripheral blood cells. This receptor was also expressed in cells of particular relevance to asthma and atopy—eosinophils, macrophages, monocytes, and B lymphocytes. 9 Ref 9, p 227, C2, ¶4; p 229, Fig 2H; p 230, Fig 4D.B; p 231, Fig 5E C2, ¶1, L1-3,6-8; p 232, L 1
  • MS Slide 7 By means of a panel of peripheral blood cell markers, the CysLT 1 receptor was found in cells of particular relevance to asthma, namely, the eosinophils, monocytes/macrophages, B lymphocytes, and CD34 + granulocytic precursor cells. 9 Human mast cells also express this receptor, 10 and eosinophils and monocytes can synthesize CysLTs. 9 The expression of the CysLT 1 receptor on both of these cell types suggests that autocrine and paracrine activation may occur after stimulation by the appropriate inflammatory signal. Expression of the CysLT 1 receptor on pregranulocytic CD34 + cells raises the possibility that CysLTs may influence the differentiation pathway of these cells under some conditions. 9 Ref 9, p 231, C2, ¶4, L1-3,6-8; p 232, L 1 Ref 10, p 7965, C1, ¶1, L1-2, C2, 1,L7,21-22 Ref 9, p 232, C1, ¶1, L1 Ref 9, p 232, C1, ¶1, L1-8
  • MS Ref 7, p S41, C1, ¶3, L1-2, C2, L3-4   Ref 7, p S38, C1, ¶2, L1-3; p S41, C1, ¶3, L1-4; p S41, C1, ¶3, L4-5 Ref 7, p S41, C2, L1-4 Slide 8 Extensive interplay between CysLTs and their receptors and other mediators and their receptors results in a self-amplifying pro-inflammatory circuit in patients with asthma. 7 CysLTs increase the production or expression of T H 2 cytokines and other mediators that contribute to asthmatic inflammation, 7 as well as the expression of receptors for other mediators, including histamine receptors. 7 Conversely, the generation and receptor expression of CysLTs can be amplified by a variety of cytokines and other mediators. 7
  • MS Slide 9 Leukotriene receptor antagonists (LTRAs) inhibit the production or expression, or both, of a variety of mediators that may contribute to asthmatic inflammation. These include not only CysLTs but also many steroid-sensitive cytokines such as tumor necrosis factor-alpha, IL-6, and adhesion molecules. 7 The broad clinical effects of LTRAs are probably attributable to their ability to interrupt the extensive interactions between CysLTs and their mediators. 7 Ref 7, p S38, C1, ¶2, L1-3 C1, ¶2, L4-6 C2, ¶1, L11-14     Ref 7, p S38,
  • MS Slide 10 Early evidence of the importance of CysLTs in asthma 11,12 was provided by their recovery in the blood, bronchoalveolar lavage (BAL) fluid, and urine of patients after spontaneous or induced bronchospasm. 12 The ability of specific LTRAs to increase airflow and reduce symptoms further supports leukotriene involvement in this disease. 12 Generated by inflammatory cells such as mast cells and eosinophils, 12 CysLTs have been correlated with Edema Increased mucus secretion and decreased mucus transport Epithelial-cell damage Smooth-muscle contraction and proliferation Recruitment of inflammatory cells, such as eosinophils, into the airway 11 In addition, CysLTs cause profound bronchoconstriction, with a potency approximately 1000 times that of histamine on a molar basis. 13 Ref 11, p 307, C2, ¶1, L1-3 Ref 12, p 272, C1, ¶1, L6-9 Ref 12, p 272, C1, ¶4, L1-4, C2, L1-2 Ref 12, p 272, C2, ¶1, L1-6 Ref 12, p 272, C1, ¶3, L1-5 Ref 11, p 308, Fig. 3; p 305, C1, ¶1, L2-4, C1, ¶3, L1-3 Ref 13, p 4, C1, ¶2, L3-6
  • MS Ref 3, p 9, C2, ¶2, L1-2; p 10, C1, ¶1, L1-3; p 12, C2, ¶1, L4-6, C2, ¶2, L6-8; p 13, Table 6; p 14, Fig. 3 Slide 3 A recent study examined the relationship between airway inflammation and disease activity in 74 non-smoking patients with intermittent (n=19), mild to moderate (n=38), or severe persistent (n=17) asthma. Twenty-two nonatopic individuals served as controls. A subanalysis was performed of patients receiving corticosteroid therapy. Patients with mild to moderate asthma showed significantly higher levels of inflammatory mediators (eosinophils) versus controls, despite treatment with high (p<0.01). 3 Thus, some degree of airway inflammation may persist despite treatment with corticosteroids at any dose.
  • MS Ref 17, p 1232, C2, ¶3, L1-2, ¶3, L1-12; p 1233, C1, ¶1, L14-15   Ref 17, p 1234, C2, ¶4 (entire); p 1236, Fig 4B (p value) Ref 17, p 1237, C2, ¶1, L1-4, ¶ 2, L1-4 Slide 15 A clinical study evaluated the effects of adding montelukast to ICS therapy in 22 patients with mild to moderate persistent asthma. During a two-week run-in, patients received one puff twice daily of a combination product containing the ICS fluticasone propionate 250 µg and the long-acting beta 2 agonist (LABA) salmeterol 50 µg. They were then randomized to three weeks of double-blind treatment with montelukast 10 mg once daily at bedtime or placebo; for the first two weeks of double-blind treatment, patients received one puff daily of the combination product, and for the last week they were switched to fluticasone 250 µg one puff twice daily. Peripheral blood eosinophil counts were measured at all visits. 17 Montelukast in combination with fluticasone significantly reduced blood eosinophils compared with ICS + LABA by 10 6 /L (p<0.05). 17 While salmeterol neither conferred discernible anti-inflammatory effects nor potentiated the anti-inflammatory effects of the ICS, the addition of montelukast to either ICS (fluticasone) or ICS + LABA (fluticasone + salmeterol) provided complementary activity against markers of asthmatic inflammation. 17
  • MS Ref 18, p 1862, C1, ¶1, L7-9, C2, ¶2, L1-5 Ref 18, p 1863, C1, ¶5, L1-6, C1, ¶6, L9-25 Ref 18, p 1864, Table 1; p 1865, C2, ¶2, L1-5 Ref 18, p 1866, C2, ¶2, L1-3; p 1867, C1, ¶ 3, L4-6 Slide 16 A clinical study was performed to determine whether the addition of an LTRA would provide complementary or additive benefits, or both, in patients with asthma incompletely controlled by inhaled beclomethasone. 18 After a four-week single-blind run-in period, during which patients received inhaled beclomethasone 200 µg twice daily and one placebo tablet once daily, randomized double-blind treatment began with Montelukast 10 mg once daily + inhaled beclomethasone 200 µg twice daily (additivity group) Inhaled beclomethasone 200 µg twice daily + placebo tablets (beclomethasone group) Montelukast 10 mg once daily and inhaled placebo twice daily (montelukast group) Placebo tablet once daily + inhaled placebo twice daily (placebo group) The first two groups received 16 weeks of double-blind treatment, whereas the latter two groups were treated for 12 weeks, because of the need to taper beclomethasone after the run-in; i.e., the morning inhaler was replaced with placebo at week 2 of double-blind treatment, and the evening inhaler was replaced with placebo at week 4. 18 Mean peripheral blood eosinophil counts were comparable at baseline across the groups: 0.23 10 3 /µl in the placebo and montelukast groups and 0.22 10 3 /µl in the beclomethasone and additivity groups. At the end of double-blind treatment, counts were significantly lower in the additivity group than in the group receiving beclomethasone alone (p=0.011). 18 The addition of leukotriene-modifying treatment to ICS therapy thus provided complementary, additive effects on peripheral blood eosinophils, a marker of asthmatic inflammation. 18
  • MS Slide 17 CysLTs and steroid-sensitive mediators are two important pathways of inflammation in asthma. 7 Corticosteroids do not block the leukotriene-mediated pathway of inflammation. 7,19 Therefore, treating dual pathways may provide complementary benefits—better control of inflammation and effective asthma control—compared with treating only the steroid-sensitive pathway. 7,19 Ref 7, p S37, C1, ¶1, L3-6; p S38, C1, ¶2, L1-3   Ref 7, p S39, C1, ¶2, L1-8 Ref 19, p 9, C1, ¶1, L3-7   Ref 7, p S37, C1, ¶ 1,L3-6 Ref 19, p 10, C2, ¶2, L1-13
  • MS Slide 18 A study examined the relationship between airway inflammation and disease activity in 74 patients with intermittent, mild to moderate, or severe, persistent asthma and 22 healthy nonatopic control subjects. Two of 19 patients with intermittent asthma, 25 of 38 with mild to moderate asthma, and 15 of 17 with severe asthma were receiving regular ICS therapy. Airway inflammation was determined through total and differential cell counts of inflammatory mediators, including absolute eosinophil counts and concentrations of eosinophilic cationic protein (ECP), in induced sputum. Disease activity was assessed by means of lung function testing (peak expiratory flow rate [PEFR] and forced expiratory volume in one second [FEV 1 ]) and self-reported symptom scoring. As the slide shows, both lung function and symptoms were positively correlated with markers of inflammation across the entire spectrum of asthma severity. 3 Ref 3, p 9, C2, ¶2, L1-2 p 10, C1, ¶1, L1-2, C1, ¶2; C2, L11-13; p 12, C2, Table 4; p 13, C1, ¶ 1, L1-5

Management of Bronchial Asthma Management of Bronchial Asthma Presentation Transcript

  • DISTINGUISHED PARTICIPANTS
  • In the Name of Allah the Most Gracious, the Most Merciful
  • MODERN TRENDS IN THE MANAGEMENT OF BRONCHIAL ASTHMA SummaryAirway inflammation is recognized as the most criticalcomponent of asthma, and this may be present even inthe absence of severe symptoms. Present day therapycomprises bronchodilators i.e. B-agonists, t heophyllineand anticholinergic, and anti inflammatory drugs i.e.Corticosteroids, Leukotrein Inhibitors and cromolyn.Inhaled corticosteroids and Leukotrein Inhibitors, are thefirst-line therapy both to prevent and control symptoms.In recommended dosages these medications are safeand well tolerated.
  • Definitions:Asthma is a complex and heterogeneous disordercharacterised by:a) Reversible airway constrictionb) Airway inflammation andc) Airway hyper-responsiveness to a wide variety ofstimuli.In asthma, there is paroxysmal bronchospasm, mucosaloedema, mucus hypersecretion, inflammatory infilterates inthe bronchial wall,bronchial epithelial damage anddesquamation, and glandular hypertrophy. The degree ofbronchial hyper-responsivences is related to the extant ofinflammation in airways.
  • Histopatholoqic Findings in Asthma:Airway inflammation is exhibited even in patientswith mild disease as seen in the following:-1) Denudation (Damage) of airway epithelium andits shedding.2) Deposition of collagen beneath the basement membrane (thicking of basement membrane).3) Mast Cell degranulation4) Oedema5) Inflammatory Cell infiltration  Eosinophils  Lymphocytes
  • Triggers of Asthma:1. Allergic - Immunological mechanisms plays important part.2. Non-allergic -without immunological mechanism. i) Infections ii) Aspirin Iii) Exercise iv) Irritants v) Occupational Exposures, vi) Emotional Upset. Both groups exhibit hyper reactive airways.
  • AIR-WAYS RESPONSE TO INHALED ANTIGEN IN ASTHMA, Fig-1
  • Inflammatory Cells:1. Mast Cells2. Eosinophils3. Epithelial Cells
  • Inflammatory Mediators:- Contribute to various features of asthmatic response.------Br: constriction, Microvascular leakage & mucus secretion.----- PG D2 and leukotrienes contribute to B.H.----- P.A.F. (Lipid Mediator) Stimulates a. Adhesion of Eosi: to vascular endothelium b. Release of Basic Proteins from Eosino. Epithelial Damage/Shedding Loss of Protective Epi. relaxing factor Bronchial Hyper responsiveness Exposes sensory nerves ----- Triggered More readily
  • Inflammatory Cells Involved in Asthma:-
  • Clinical Features of Asthma:- MILD MODERATE SEVERESymptoms Intermittent Chronic Continuous brief symptoms >2 times/week < 1-2 times/weekActivity/ Normal Affected Affected &Sleep LimitedNocturnal < 1-2 times/month > 2 times / month FrequentAsthmaSymptomsBetween Asymptomatic +/- FrequentExacerbations exacerbationsPEFR or FEV 1 > 80% predicted 60 - 80 % of < 60% predicted predictedPEFRorFEVI < 20% 20-30% > 30%VariabilityB-Agonists --- + ++daily requirement
  • Management of Asthma:- Control of Asthma means:-1. Minimal chronic symptoms including nocturnal symptoms2. Minimal exacerbations.3. Minimal or no need for B2 agonists.4. Normal activities, including exercise, can be undertaken.5. PEF circadian variation < 20%6. Near Normal PEF.7. Minimal or no adverse effects from medication. Asthma may be mild, moderate or severe.
  • Management of Bronchial Asthma:-a. Bronchodiators SOSb. Anti Inflammatory Drugs i) Steroid ii) Anti Leukotriene
  • Bronchodilator Drugs:-a. B-Adrenergic Agonist drugs.b. Methylxanthines (Theophylline),c. Anticholinergic Drugs.
  • B-adrenergic Agonist Drugs:-Mode of Action:-B-adrenergic agents —> stimulate enzyme adenyl cyclase —> which converts ATP intocyclic AMP. This increase of cyclic AMP leads to activation of protein kinase A, whichinhibits the phosphorylation of myosin and lowers intracellular ionic calciumconcentration, resulting in relaxation. B-Adrenergic agonists relax smooth muscle of allairways, from trachea to terminal bronchioles. B-Adrenergic agonists may inhibit the release of mediators from mast cells in the airways and release ofacetylcholine from postganglionic cholinergic nerves in the airways.B-Adrenergic agonists do not inhibit either the late response to allergens or thesubsequent brochial hyper-responsiveness. These actions may be related to the factthat B-Adrenergic agonists do not have an inhibitory effect on inflammatory cells thathave been implicated in both the late reponse and bronchial hyperresponsiveness.Clinical Use:-Sympathomimetics: L.A. = Long Acting i) Salbutamol (Ventolin) ii) Terbutaline(Bricanyl) iii) Fenoterol (Berotec) iv) Formoterol (L.A) v) Salmeterol (L.A) vi) TulobuterolBreemax(L.A)vii) Rimiterol(Pulmadil) viii) Porbuterol (Exirel)ix) Reproterol (Bronchodil). x) Others
  • Methylxanthines Theophylline:a. Mechanism of Actionb. Dosage and Clinical Use
  • Anti Inflammatory Drugs:-1. Cortico Steroids2. Cromolyn Sodium3. Leukotreins Inhibitors
  • Corticosteroids:-a. Effect on inflammatory & Airway Cellsb. Effect on Asthmatic Inflammationc. Effect on Air-way Hyper Responsiveness
  • Inhaled steroids and Dosages:-1. First Line Therapy for Chronic Asthma.2. Steroids required to control asthma in majority of Adults3. Doses upto 800 ug daily in adults and 400 ug daily in children are safe.4. Twice daily administration of inhaled steroids are quite effective.5. Orally administered steroids, such as prednisolone ormethylpredinsolone, are still required to control Asthma insome patients, but then there is risk of side effects, with dailydose exceeding 10 mg.
  • Guidelines for Oral Steroid Therapy are:-1. Start with high doses for exacerbation (e.g. prednisolone 30-60 mg/day). Dose will depend upon extent of exacerbation, and patients oral maintenance dose.2. After control of symptoms, tapper rapidly (within 5-7 days) to baseline steroid dose.3. For "Chronic" patients, try to keep daily dose of prednisolone below 10 mg/day.4. Give daily morning dose only. This will eliminate or reduce the suppression of hypothalamic pituitary-adrenal axis (HPA axi).5. Attempt alternate-day steroids if more than 7.5mg prednisolone/day is required. Then "On" days initial dose is to be 2-3 times.6. Use beclomethasone dipropionate aerosol or otherinhaled steroids alongwith for ultimately eliminating or reducing dose of oral prednisolone.
  • Asthma Therapy:- MILD MODERATE SEVERECORTICOSTEROIDSInhaled _ +200 to 1000 ug +800 to 1400 ugOral _ _ +Parenteral _ _ +CROMOLYN +/- +/- _B-AGONISTSInhaled + + +Oral + + +THEOPHYLLINE _ +SR + SR
  • Importance of Inflammation in AsthmaAdapted from National Institutes of Health Global Initiative for Asthma: Global Strategy for Asthma Management andPrevention: A Pocket Guide for Physicians and Nurses. Publication No. 95-3659B. Bethesda, MD: National Institutesof Health, 1998; Bjermer L Respir Med 2001;95:703-719.
  • Leukotrienes: Important in Early Asthma and Throughout the Disease Other inflammatory mediators Leukotrienes No Inflammation Asthma InflammationAdapted from Holgate ST, Peters-Golden M J Allergy Clin Immunol 2003;111(1 suppl):S1-S4; Holgate ST et al J AllergyClin Immunol 2003;111(1 suppl):S18-S36; Henderson WR Jr et al Am J Respir Crit Care Med 2002;165:108-116; Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42; Varner AE, Lemanske RF Jr. In Asthma andRhinitis. Oxford, UK: Blackwell Science, 2000:1172-1185.
  • Dual Pathways of Inflammation Effects of the CysLT1 Receptor on Inflammatory CellsLung Macrophage Eosinophils Smooth- muscle cell Monocytes PBMC CysLT=cysteinyl leukotriene; PBMC=peripheral blood mononuclear cells Adapted from Figueroa DJ et al Am J Respir Crit Care Med 2001;163:226-233.
  • Dual Pathways of Inflammation Expression of the CysLT1 Receptor CD19 LN5 B Lymphocyte Macrophage Mast Cell M-CSF LTC4 Basophil LTD4 CysLT1R GM-CSF LTE4 M-CSF, GM-CSF, IL-3 CD14 LTC4, LTD4, LTE4 Monocyte IL5Rβ IL-5 CD34+ IL-3 Neutrophil Pluripotent GM-CSF LTC4 CCR3 hemopoietic LTE4 LTD4 stem cell T Cells Eosinophil Represents the CysLT1 receptor CD4+ CD8+Adapted from Figueroa DJ et al Am J Respir Crit Care Med 2001;163:226-233; Mellor et al Proc Natl Acad Sci USA 2001;98:7964-7969
  • Dual Pathways of InflammationLeukotrienes Are Powerful Inflammatory Mediators CysLT Other Mediator CysLTreceptor mediators receptor Adapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(suppl 1):S37-S48.
  • Dual Pathways of Inflammation Actions of LTRAsLeukotrienes are highly specific but catalyzea massive inflammatory cascade  Suppress many inflammatory mediators  Suppress inflammatory processes  Via the leukotriene pathway  Via the steroid-sensitive pathway LTRAs = leukotriene receptor antagonists Adapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(suppl 1):S37-S48.
  • Dual Pathways of Inflammation Central Role of CysLTs in Asthma Decreased Mucus Transport Cationic Protein Release, Epithelial-Cell Damage AirwayEpithelium Eosinophil Sensory Increased Influx Nerves Mucus (C fibers) Secretion Contraction and Edema CysLTs Proliferation Blood Vessel Inflammatory Cells Airway Smooth Muscle (mast cells, eosinophils) Adapted from Hay DWP et al Trends Pharmacol Sci 1995;16:304-309.
  • Airway Inflammation Persisted Despite Corticosteroid UseIn a clinical study of 74 patients p<0.01 p<0.001 20,000 10,000 p<0.001 p<0.01 1,000Eosinophil × 103/g sputum 100 10 1 Control ICS ICS OCS OCS ± ICS group low-dose high-dose (n=10) (n=7) (n=10) (n=15) Mild to moderate Severe asthmaICS=inhaled corticosteroids; OCS ± ICS=received oral corticosteroids with or without ICSAdapted from Louis R et al Am J Respir Crit Care Med 2000;161:9-16.
  • Dual Pathways of Inflammation Long-Acting Beta2 Agonists Did Not Have Anti-inflammatory EffectsLTRA montelukast further reduced inflammation whenadded to ICS ICS + LABA + ICS + ICS + Montelukast Montelukast LABA ICS 0Change ineosinophils (× 106/L) –100from run-in –200 p<0.05 p<0.05 LABA = long-acting beta2 agonist Adapted from Currie GP et al Am J Respir Crit Care Med (in press).
  • Dual Pathways of Inflammation LTRA Montelukast Further Reduced Asthmatic Inflammation Complementary therapy that targets dual pathways of inflammation provided better control of inflammation 0.12 * 0.10 Eosinophil 0.08 counts (change 0.06from baseline × 103/µl) 0.04 0.02 <1* 0 Placebo Montelukast Beclomethasone Montelukast + beclomethasone Treatment group *p<0.05 compared with beclomethasone Adapted from LaViolette M et al Am J Respir Crit Care Med 1999;160:1862-1868.
  • Dual Pathways of Inflammation Montelukast Combined with a Steroid Affects the Dual Pathways of Inflammation CysLTs Steroid-sensitive play a key role mediators in asthmatic play a key role inflammation in asthmatic inflammation Steroids do NOT inhibit CysLT formation in the airways of asthmatic patients Montelukast Inhaled steroids blocks the block effects of steroid- CysLTs sensitive mediators DUAL PATHWAYAdapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42; Bisgaard H Allergy 2001;56(suppl 66):7-11.
  • Dual Pathways of Inflammation Airway Inflammation Correlated with Lung Function and Clinical Control PEFR Daily symptom FEV1 variability score 0 –0.2 rS –0.4 –0.36 –0.43 –0.49 –0.51 –0.51 –0.52 –0.6 Absolute eosinophil counts ECP concentrationsFEV1 = forced expiratory volume in one second; PEFR = peak expiratory flow rate; rS = Spearman’s rank coefficient ofcorrelation; ECP = eosinophilic cationic proteinAdapted from Louis R et al Am J Respir Crit Care Med 2000;161:9-16.
  • Leukotriene Inhibitor:- Montelukast
  • Leukotriene Inhibitor:- Montelukast 5mg / 10mg Tablets (Montelukast) blocks cystienyl, receptors in human airwaysinhibiting LTD4 leukotriene attachment to these receptors leading to: 1. Minimized airway odema (Bronchial smooth muscles relaxation) 2. Minimized mucus secretion (By inhibiting the inflammation process)(Montelukast) Provides significant relief from symptomsof allergic rhinitis while also conferring a benefit for asthma inpatients with both allergic rhinitis and asthma.(Montelukast) administered once daily improved efficacywas well tolerated in pediatric patients with chronic persistentasthma establishing itself as a valuable treatment option to currentasthma therapies in 6 to 14 years old patients.
  • Others:1. Cromolyn Sodium2. Ketotifen3. Methotraxate4. Gold
  • ACUTE SEVERE ASTHMA – LIFE THREATENING
  • Clinical1. Increased dyspnoea, fatigue, and stage of exhaustion.2. Altered mental state; cannot complete sentences.3. Increased bronchodilator needs.4. History of previous severe asthma attack.5. Recent upper respiratory tract infection – viral or bacterial.6. A more persistent obstruction due to mucus impaction.
  • Signs & Criteria1. Cyanosis2. Pulse rate > 120/minute3. Pulses paradoxus greater than 18-20 mmHg.4. Silent chest5. PEFR below 100/L minute or PEVI less than 0.5L, and failure to improve with bronchodilators.6. PaO2< 60 mmHg.7. PacO2 > mmHg.8. Low blood pH.9. Low serum Potassium.10. ECG – P Pullmonate.
  • Possible Complications.1. Mucus Plugging.2. Tension pneumothorax or pneumoperitoneum.3. Pulmonary oedema.4. Massive pulmonary collaspe.5. Arrhythmias.6. Hypovolemia.
  • ACUTE SEVERE ASTHMA – LIFE THREATENING ATTACK IN ADULTS
  • TREATMENT1. I.V. route established.2. Oxygen by mask 6 L/min. & continue.3. High dose of Beta2 – agonist given & repeat every 20 minutes during 1st hour – preferably by nebulizer (10-15 puffs by spacer if nebulizer not available) – Repeat 4 hourly.4. Salbutamol subcut :/I.V.5. Oral prednisolone 30-60 mg or I.V. hydrocortisone 200 mg. & repeat 4 hourly.6. Slow I.V. aminophylline 250 mg. (if not taken orally)7. Arrange hospialization.8. If danger of imminent arrest – mechanical ventalation/oxygen mask +.
  • Conclusion:- SummaryTargeting Dual Pathways of Inflammation Improves Asthmacontrol1. Drug Inhalation is better than oral Administration2. Mild Asthmatics-Inhaled B2-Adrenergic against may be enough.3. Chronic Asthma-Anti Inflammatory Therapy must be introduced earlier.4. Cys LTs and steroid-sensitive mediators are two important pathway of inflammation in asthma5. Corticosteroids do not block the leukotriene-mendiated pathway of inflammation6. Treating dual pathways of inflammation in the airway of asthmatic patients may provide better control of inflammation and effective asthma control