Asthma 01 Dr Mazen Qusaibaty MD DIS Head

Asthma 01 Dr Mazen Qusaibaty MD, DIS / Head Pulmonary and Internist Department Ibnalnafisse Hospital Ministry of Syrian health – Email: Qusaibaty@gmail. com

G lobal INitiative for A sthma © Global Initiative for Asthma

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Definition of Asthma

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

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

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

8 Burden of �Prevalence Asthma of Asthma

Burden of Asthma report 9

~ individuals 2004 300 million a f f e c t e d 2025 : ~ 400 million �~ 5 % yearly

11 Billion $ Direct Costs Asthma $11. 5 National Heart Lung and Blood Institute. Morbidity and Mortality Chartbook. Bethesda, MD: US Department of Health and Human Services; 2004.

12 Billion $ Indirect Costs Asthma $4. 6 National Heart Lung and Blood Institute. Morbidity and Mortality Chartbook. Bethesda, MD: US Department of Health and Human Services; 2004.

13 Billion $ Direct Costs Indirect Costs Total Costs Asthma $11. 5 $4. 6 $16. 1 National Heart Lung and Blood Institute. Morbidity and Mortality Chartbook. Bethesda, MD: US Department of Health and Human Services; 2004.

1 i n e v e r y 250 deaths worldwide � Asthma Masoli M, Fabian D, Holt S, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee 14 report. Allergy 2004; 59: 469

Severe Asthma Airway remodeling 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 Fixed airway obstruction

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ASM Ep Ep SMG Nonasthmatic control M ASM SMG Patient with fatal asthma

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

19 Nonasthmatic control Small airways Patient with fatal asthma

Appearance at post mortem Macroscopic aspect of the lungs in fatal asthma The lung is hyperinflated Did not collapse on opening the thoracic cage 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 Cross-section of a large cartilaginous bronchus The lumen is filled with a very viscous mucous plug 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)

Allergen Antigen presenting cells (APCs)

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

Allergen Th 2 cell Antigen presenting cell Lymphocyte Activation (Activation of Th 2 -cells) (CD 4+/CD 25+ state)

Allergen IL-4 IL-13 Th 2 cell IL-5 Antigen presenting cell TH 2 release of specific ILs and cytokines responsible for episodic and chronic allergic reactions

Ig. E B cell Allergen IL-4 IL-13 Th 2 cell IL-5 Antigen presenting cell IL- 4 enhances the synthesis of Ig. Es by antigen stimulated B lymphocytes (plasma cells)

Ig. E Fce. RI B cell Allergen Mast cell IL-4 IL-13 Th 2 cell Histamine Leukotrienes Prostaglandins Cytokines Atopic disease IL-5 Antigen presenting cell Ig. E binding to receptors on mast cells mast cell activation and the release of inflammatory mediators

Ig. E 15 – 30 min Fce. RI Immediate Phase B cell Allergen Mast cell IL-4 IL-13 Th 2 cell Histamine Leukotrienes Prostaglandins Cytokines IL-5 Antigen presenting cell Acute Allergic Response Atopic disease

Ig. E Fce. RI Immediate Phase B cell Allergen Mast cell IL-4 IL-13 Th 2 cell Antigen presenting cell 15 – 30 min Histamine Leukotrienes Prostaglandins Cytokines Atopic disease IL-5 Eosinophil IL-5 plays an important role in the recruitment of eosinophils to the site of inflammation

Ig. E Fce. RI Immediate Phase B cell Allergen Mast cell IL-4 IL-13 Th 2 cell Antigen presenting cell 15 – 30 min Histamine Leukotrienes Prostaglandins Cytokines Atopic disease 6 – 8 hours IL-5 Delayed Phase Eosinophil The eosinophil releases mediators with a range of tissue-destructive effects

Asthma Inflammation: C e l l s a n d Mediators 33 Source: Peter J. Barnes, MD

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35 Risk factors for asthma • Gender

Girls < Boys in childhood www. cdc. gov/asthma/NHIS/06/Data. htm (Accessed on December 16, 2008).

Girls > Boys at puberty 37 www. cdc. gov/asthma/NHIS/06/Data. htm (Accessed on December 16, 2008).

Girls = Boys by early adulthood www. cdc. gov/asthma/NHIS/06/Data. htm

Women > Men by age 40 www. cdc. gov/asthma/NHIS/06/Data. htm

40 Risk factors for asthma • Early Abnormalities In Pulmonary Function

41 • Familial Risk factors for asthma History of 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 45 Journal of Asthma and Allergy 2015: 8 51– 61

�Mother’s age at onset of asthma 10 years ye ars �the risk of asthma for the offspring 1. 37 -fold 46 Journal of Asthma and Allergy 2015: 8 51– 61

47 Risk factors for asthma • Atopy and Allergens

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.

1/3 of children w i t h Atopic Dermatitis � Asthma 49 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 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. 50 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.

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

52 Risk factors for asthma • Obesity

o Patients with an elevated BMI are at increased risk for developing 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 Risk factors for asthma Perinatal Factors

Increased Ig. E 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 Ig. E levels. A follow-up at the age of 5 years. Cord blood Ig. E. IV. Pediatr Allergy Immunol 1993; 4: 34

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

�Maternal age � Infant mortality due to respiratory illnesses � Wheezy illness 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

Maternal diet during pregnancy Z vit inc am in D an tio vit x am ida ins nt E Martindale S, Mc. Neill 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.

Breastfeeding � Asthma 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

Neonatal jaundice The rate of asthma was higher 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 t h e 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 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 64

Prenatal exposure to maternal smoking �the risk for wheezing � Asthma 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 65

66 ¶Passive smoking is dangerous ¶Parents should not smoke