Dr Mazen Qusaibaty MD, DIS / Head Pulmonary and Internist Department Ibnalnafisse Hospital Ministry of Syrian health – Dr Mazen Qusaibaty MD, DIS / Head Pulmonary and Internist Department Ibnalnafisse Hospital Ministry of Syrian health – Asthma 01

G IN A lobal itiative for sthma lobal itiative for sthma © Global Initiative for Asthma

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Definition Asthma Definition of Asthma

Asthma Heterogeneous Disease Asthma is a Heterogeneous Disease Chronic Airway Inflammation Usually characterized by Chronic Airway Inflammation

Definition of asthma It is defined by the history of respiratory symptoms such as: It is defined by the history of respiratory symptoms such as:  Wheeze  Shortness of breath  Chest tightness  Cough

Characters of Respiratory symptoms Respiratory symptoms Variable Time Intensity Expiratory airflow limitation

Burden Asthma Burden of Asthma 8  Prevalence Asthma  Prevalence of Asthma

Burden of Asthma report 9

2004 ~ 300 million 2004 ~ 300 million affected individuals 2025 : ~ 400 million  ~ 5 % yearly

11 Direct Costs Billion $ $11.5Asthma National Heart Lung and Blood Institute. Morbidity and Mortality Chartbook. Bethesda, MD: US Department of Health and Human Services; 2004.

12 Indirect Costs Billion $ $4.6Asthma National Heart Lung and Blood Institute. Morbidity and Mortality Chartbook. Bethesda, MD: US Department of Health and Human Services; 2004.

13 Total Costs Indirect Costs Direct Costs Billion $ $16.1$4.6$11.5Asthma National Heart Lung and Blood Institute. Morbidity and Mortality Chartbook. Bethesda, MD: US Department of Health and Human Services; 2004.

1 250 deaths worldwide  Asthma 1 in every 250 deaths worldwide  Asthma 14 Masoli M, Fabian D, Holt S, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004; 59:469

Severe Asthma Airway remodeling Fixed airway obstruction Death Limb SL, Brown KC, Wood RA, et al. Irreversible lung function deficits in young adults with a history of chilhood asthma. J Allergy Clin Immunol 2005; 116:1213

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Patient with fatal asthma Nonasthmatic control ASM Ep SMG M

18 Ep ASM SMG BM  Epithelial damage  Basement Membrane (BM) thickening  Airway Smooth Muscle (ASM) layer is thickened

19 Small airways Nonasthmatic control Patient with fatal asthma

Appearance at post mortem Holloway L, Beasley R, Roche W. The pathology of fatal asthma. In: Busse WB, Holgate ST, eds. Asthma and Rhinitis. Boston, Blackwell Scientific Publications, 1995; pp. 109–118

Appearance at post mortem Holloway L, Beasley R, Roche W. The pathology of fatal asthma. In: Busse WB, Holgate ST, eds. Asthma and Rhinitis. Boston, Blackwell Scientific Publications, 1995; pp. 109–118

Pathophysiology Type 1 Hypersensitivity (immediate hypersensitivity)

Antigen presenting cell Allergen Antigen presenting cells (APCs)

Antigen presenting cell Allergen Antigen penetrates beneath the mucosa and enters the lymphatic system

Th2 cell Antigen presenting cell Allergen Lymphocyte Activation (Activation of Th2-cells) (CD4+/CD25+ state)

Th2 cell IL-4 IL-13 IL-5 Antigen presenting cell Allergen TH2 release of specific ILs and cytokines responsible for episodic and chronic allergic reactions

Th2 cell B cell IL-4 IL-13 IgE IL-5 Antigen presenting cell Allergen IL- 4 enhances the synthesis of IgEs by antigen stimulated B lymphocytes (plasma cells)

Th2 cell B cell IL-4 IL-13 Mast cell FceRI IgE Histamine Leukotrienes Prostaglandins Cytokines Atopic disease IL-5 Antigen presenting cell Allergen IgE binding to receptors on mast cells mast cell activation and the release of inflammatory mediators

Th2 cell B cell IL-4 IL-13 Mast cell FceRI IgE Histamine Leukotrienes Prostaglandins Cytokines Atopic disease IL-5 Antigen presenting cell Allergen Immediate Phase 15 – 30 min Acute Allergic Response

Th2 cell B cell Eosinophil IL-4 IL-13 Mast cell FceRI IgE Histamine Leukotrienes Prostaglandins Cytokines Atopic disease IL-5 Antigen presenting cell Allergen Immediate Phase 15 – 30 min IL-5 plays an important role in the recruitment of eosinophils to the site of inflammation

Th2 cell B cell Eosinophil IL-4 IL-13 Mast cell FceRI IgE Histamine Leukotrienes Prostaglandins Cytokines Atopic disease IL-5 Antigen presenting cell Allergen Immediate Phase 15 – 30 min 6 – 8 hours Delayed Phase The eosinophil releases mediators with a range of tissue-destructive effects

Asthma Inflammation: Cells and Mediators 33 Source: Peter J. Barnes, MD

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35 GenderGender Risk factors for asthma

(Accessed on December 16, 2008). Girls < Boys childhood Girls < Boys in childhood

37 (Accessed on December 16, 2008). Girls > Boys puberty Girls > Boys at puberty

Girls = Boys Girls = Boys by early adulthood

Women > Men Women > Men by age 40

40 Early Abnormalities In Pulmonary FunctionEarly Abnormalities In Pulmonary Function Risk factors for asthma

41 Familial History AsthmaFamilial History of Asthma Risk factors for asthma

The impact of parental history on children’s risk of asthma

Journal of Asthma and Allergy 2015:8 51–61

Maternal asthma history was strongly associated with the onset of asthma in the second generation 44 Journal of Asthma and Allergy 2015:8 51–61

Children whose mother had an earlier age of onset had an increased risk of 3.71 Children whose mother had an earlier age of onset had an increased risk of Journal of Asthma and Allergy 2015:8 51–61

 Mother’s age at onset of asthma 10 years  the risk of asthma for the offspring 1.37-fold 46 Journal of Asthma and Allergy 2015:8 51–61

47 Atopy AllergensAtopy and Allergens Risk factors for asthma

Adults with Rhinitis  Asthma Shaaban R, Zureik M, Soussan D, et al. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet 2008; 372:1049.

Sensitization to Indoor Allergens is strongly associated with Asthma 50 latts-Mills TA. How environment affects patients with allergic disease: indoor allergens and asthma. Ann Allergy 1994; 72:381/Porsbjerg C, von Linstow ML, Ulrik CS, et al. Risk factors for onset of asthma: a 12-year prospective follow-up study. Chest 2006; 129:309/ Sporik R, Chapman MD, Platts-Mills TA. House dust mite exposure as a cause of asthma. Clin Exp Allergy 1992; 22:897.

Exposure to Bacteria and Bacterial Products May influence the development of allergen sensitization and asthma

52 ObesityObesity Risk factors for asthma

Egan KB, Ettinger AS, Bracken MB. Childhood body mass index and subsequent physician-diagnosed asthma: a systematic review and meta- analysis of prospective cohort studies. BMC Pediatr 2013; 13:121

54 Pre- and Perinatal FactorsPre- and Perinatal Factors Risk factors for asthma

Increased IgE levels in infant cord blood + Family history of atopy Are associated with the development of atopic disease in childhood Hansen LG, Halken S, Høst A, et al. Prediction of allergy from family history and cord blood IgE levels. A follow-up at the age of 5 years. Cord blood IgE. IV. Pediatr Allergy Immunol 1993; 4:34

Development of atopic disease in childhood Maternal age Maternal diet during pregnancy Breastfeeding Prematurity Mode of delivery

57 Martinez FD, Wright AL, Holberg CJ, et al. Maternal age as a risk factor for wheezing lower respiratory illnesses in the first year of life. Am J Epidemiol 1992; 136:1258./Infante-Rivard C. Young maternal age: a risk factor for childhood asthma? Epidemiology 1995; 6:178..

Medical Team Role 58

Zinc vitamin D Martindale S, McNeill G, Devereux G, et al. Antioxidant intake in pregnancy in relation to wheeze and eczema in the first two years of life. Am J Respir Crit Care Med 2005; 171:121. Maternal diet during pregnancy antioxidant vitamins antioxidant vitamins E

J Pediatr 2001 Aug;139(2):261-6/Am J Epidemiol 2001 Jul 15;154(2):115-9

Jaakkola JJ, Ahmed P, Ieromnimon A, et al. Preterm delivery and asthma: a systematic review and meta-analysis. J Allergy Clin Immunol 2006; 118:823

Ku MS, Sun HL, Sheu JN, et al. Neonatal jaundice is a risk factor for childhood asthma: a retrospective cohort study. Pediatr Allergy Immunol 2012; 23:623

Encouraging Normal Vaginal Delivery Encouraging the Normal Vaginal Delivery Tollånes MC, Moster D, Daltveit AK, Irgens LM. Cesarean section and risk of severe childhood asthma: a population-based cohort study. J Pediatr 2008; 153:112.

Prenatal exposure to maternal smoking  Pulmonary function in the infant 64 Hanrahan JP, Tager IB, Segal MR, et al. The effect of maternal smoking during pregnancy on early infant lung function. Am Rev Respir Dis 1992; 145:1129

Prenatal exposure to maternal smoking  the risk for wheezing  Asthma 65 Tager IB, Hanrahan JP, Tosteson TD, et al. Lung function, pre- and post-natal smoke exposure, and wheezing in the first year of life. Am Rev Respir Dis 1993; 147:811

66  Passive smoking is dangerous  Parents should not smoke