Somkiat Wongtim Professor of Medicine Division of Respiratory Disease and Critical Care Chulalongkorn University

Somkiat Wongtim Professor of Medicine Division of Respiratory Disease and Critical Care Chulalongkorn University

Asthma-related Comorbidities Comorbid conditions of the upper airways Rhinitis and Sinusitis Vocal cord dysfunction Comorbid condition of lower airways COPD Bronchiectasis (ABPA) Gastroesophageal reflux disease Obesity Obstructive sleep apnea Psychological disorders Respiratory infections Other conditions

Rhinitis Prevalence of rhinitis in asthmatic patients: increase Asthma and AR frequent coexist in the same pt. AR subject increased risk of developing asthma 20 50% of patients with AR have asthma > 80% of Asthmatic patients have AR AR also contribute to uncontrolled asthma

BHR and AR Cirillo et al. performed methacholine challenge in 342 patients with AR alone 6.4% : severe BHR 21.6% : mild BHR 56.2% : boderline BHR 15.8% : negative methacholine test AR > 5 year and FEV1 < 865 of predicted significantly associated with sever BHR

Sinusitis and Rhinosinusitis Chronic rhinosinusitis (CRS) with or without nasal polyps Up to 75% of asthmatic patients have chronic symptoms of rhinosinusitis When assessed by CT scan of sinus, up to 84% of severe asthma have evidence of sinusitis Prevalence of asthma in CRS 11 42%

Mechanism United airways hypothesis One airway, one disease concept Upper and lower airways are both manifestation of the same inflammatory process AR patients without asthma subclinical lower airways and inflammatory changes, increase BHR Several mechanism have been proposed

Two most accepted mechanisms Increased oral breathing AR: impaired filtering and air-conditioning function of the nose leading to mouth breathing resulting in increased exposure of lower airway to allergen and other asthmatic triggers Systemic response Inflammatory changes with the release of mediators into the airways and circulation which may play important role in the naso-bronchial interaction

Treatment of AR The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines Combined strategy to treat upper and lower airway diseases Leukotriene-receptor antagonist: montelukast act on upper and lower airway concommitent improvement of both AR and asthma Corticosteroids Anti-IgE; omalizumab in severe allergic AR and asthma

Gastroesophageal reflux disease Asthmatic patients have been found to have a greater risk of GERD-related symptoms Patients with GERD have risk of asthma The prevalence of GERD in asthma 12 85% of asthmatic patients GERD symptoms are reported in 50 80% of asthmatic patients In Chulalongkorn Hospital: prevalence of GERD in asthmatic patients 38% and associated with severity of asthma control by ACT

Obesity Obesity increase worldwide and associated with an increase prevalence of asthma Specific asthma phenotype Associated with low lung volume breathing Less eosinophilic inflammatory process Asscoiated with OSA and GERD Reduced response to asthma medication: especially reduced response to ICS

Obstructive sleep apnea OSA frequent associated with obesity OSA also increase BHR OSA associated with asthma in various ways upper inflammatory process that influence lower airways OSA associated with GERD effect on asthma

OSA and Asthma Mehra et al. found that IL-6, proinflammatory mediators secreted by T cell and macrophage is increased in obese patients and OSA patients OSA cause oxidative stress and inflammation in lower airway Lafond et al found CPAP treatment in OSA with asthma improved asthma symptoms, reduced bronchodilator use, improved PEFR and quality of life

Psychological Disorders Psychological disorders and stressful conditions have been shown to influence asthma control Anxiety, depression and panic disorders are more frequent in asthmatic patients than general population Depression affect asthma control by reducing adherence to the treatment and follow-up Dyspnea correlated with anxiety state Stress modulate immune function and increase prevalence of infection

Respiratory Infections Viral infection are common cause of asthma exacerbations Bacteria, Mycoplasma pneumoniae and Chlamydia pneumoniae involve asthma exacerbations and long term reduction in LFT Fungal infection: Allergic Bronchopulmaonary Aspergillosis (ABPA) typical associated with severe asthma, eosinophilia, high IgE level, central bronchiectasis, positive skin test and serum precipitins to Aspergillus

Other Comorbidities COPD: hybrid condition between asthma and COPD in smoking asthmatic patients Asthma and COPD sometimes difficult to differentiate Vocal cord dysfunction Hormonal and Metabolic disorders Early menarche had lower lung function and more asthma Metabolic syndrome Diabetes, Thyroid disease Other conditions: Atopy, Atopic dermatitis

Prevalence of GERD in Asthma in Thailand การศ กษาหาความช กของ GERD ในผ ป วย โรคห ด 56 ราย โดยใช 24 hr ph monitoring ท โรงพยาบาลจ ฬา Prevalence 37.50% 15 pts (71.43%) had GERD symptoms ถ าใช อาการในการว น จฉ ย GERD Sensitivity 71.43%, Specificity 77.14%, Positive predictive value 65.22%, Negative predictive value 81.82%

GERD is a condition which develops when the reflux of GERD stomach -content New causes Definition troublesome symptoms and / or complications Esophageal Syndromes Extra-esophageal Syndromes Symptomatic Syndromes Syndromes with Esophageal Injury Established Association Proposed Association Typical reflux syndrome Reflux chest pain syndrome Reflux esophagitis Reflux stricture Barrett's esophagus Adenocarcinoma Reflux cough Reflux laryngitis Reflux asthma Reflux dental erosions Sinusitis Pulmonary fibrosis Pharyngitis Recurrent otitis media Vakil et al. Can J Gastroenterol 2005

Causes of increased exposure of the esophagus to gastric refluxate LES dysfunction Defective esophageal clearance Hiatal hernia Delayed gastric emptying Increased intraabdominal pressure Katzka & DiMarino 1995

Endoscopy : Reflux esophagitis

Esophageal Manometry Water Perfused Manometry System High Resolution Manometry System Gonlachanvit-GERD 20

24 hour esophageal ph monitoring Gonlachanvit-GERD 21

Uncontrolled Asthma and GERD The association between GERD and level of asthma control by ACT score at KCMH GERD in uncontrolled asthma prevalence 51.17% GERD in partly controlled asthma prevalence 25.72% Asthma with ACT score < 20 (poorly controlled asthma GERD prevalence 80.89% Wongtim S., et al 2009

Difficult Asthma and GERD Leggett et al. study prevalence of GERD in difficult asthma Prevalence of GERD 75% Abnormal acid at distal esophageal ph probe prevalence 55% Proximal probe prevalence 34.6% Abnormal ph in asymptomatic GERD 9.6%

Uncontrolled Asthma and GERD Wongtim et al studied the association between GERD and level of asthma control by ACT score GERD in uncontrolled asthma prevalence 51.17% GERD in partly controlled asthma prevalence 25.72% Asthma with ACT score < 20 (poorly controlled asthma GERD prevalence 80.89%

Possibility: increased GERD in Asthma Incompetent lower esophageal sphincter (LES) Inefficient esophageal clearance Delayed gastric emptying time Increased pressure gradient between abdomen and thorax Autonomic dysregulation Lung hyperinflation Asthmatic drugs

Mechanism of GERD in Asthma Inflammation Edema Microaspiration Mediator release Mucus Reflux Inflammation BHR Smooth muscle Esophageal vagal afferent CNS Vagal reflex

Mean FEV1 (L) Mean FEV1 at baseline, 1 and 2 month after treatment GERD 2.4 2.3 2.36±0.58 2.2 2.1 2.20±0.64 FEV1 2 1.99±0.56 1.9 1.8 0 1 2 Time (Month) P< 0.001 between group

Mean PEF (L/min) Mean PEF at baseline, 1 and 2 month after treatment GERD 450 400 350 300 338.64±109.60 365.0±103.0 399.47±101.79 PEF 250 200 0 1 2 Time (Month) P<0.001 between group

Mean ACT Mean ACT at baseline, 1 and 2 month after treatment GERD 26.8 21.8 16.8 11.8 16.36±3.97 20.82±3.30 23.00±1.69 ACT 6.8 1.8 0 1 2 Time (Month) P< 0.001 between group

Compare to previous studies Study Pt no. Duration (week) Med dose (mg/day) Daytime Nocturnal PEF FEV1 FVC ACT Teichtahl et al. 1996 Kilijander et al.1999 Harding et al.1996 20 4 Ome 40 - NA + - NA NA 52 8 Ome 40 - + - - NA NA 30 8 Ome 40 +/- NA +/- +/- NA NA Toni et al.1999 57 8 Ome 40 - + - - NA NA Bhavneesh S et al. 2007 Wongtim S et al. 2010 99 16 Ome 40 + + + + NA NA 22 8 Ome 40 NA NA + + + +

Conclusion Common Comorbidity Rhinitis Sinusitis and Rhinosinusitis Gastroesophageal reflux disease +/- Obesity

Possible Comorbidity Hypertension Diabetes Ischemic heart disease Degenerative arthritis Cardiac arrhythmia Congestive heart failure Atherosclerosis CVA

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