Post on 14-Feb-2019
Caterina Mengoli (PV) Giusi Lorusso, Cecilia Susca (BA)
Università di Pavia
MALATTIE RESPIRATORIE E MALATTIA DA REFLUSSO
GASTROESOFAGEO
GERD: DEFINITION
Vakil et al, Am J Gastroenterol 2006
GERD is a condition which develops when the reflux of stomach contents causes
troublesome symptoms and/or complications
GERD: DEFINITION
Vakil et al, Am J Gastroenterol 2006
GERD: DEFINITION
Vakil et al, Am J Gastroenterol 2006
Typical reflux syndrome
HEARTBURN
REGURGITATION
Extraesophageal reflux syndromes
NON CARDIAC CHEST PAIN DYSPHAGIA
Atypical reflux syndrome
CHRONIC COUGH
LARYNGITIS
PHARYNGITIS
ASTHMA
Syndromes with esophageal injury
REFLUX ESOPHAGITIS
REFLUX STRICTURE
BARRETT’S ESOPHAGUS
ESOPHAGEAL ADENOCARCINOMA
GERD: EPIDEMIOLOGY
Loiano-Monghidoro Study
< twice/wk >twice/wk
Prevalence and frequence of typical GERD symptoms
Prev
alen
ce %
esophagitis Barrett’s esophagus
Prev
alen
ce %
Prevalence of oesophageal injury
12.1
1.2
Grade I
Grade II Grade III Grade IV
Zagari et al, Gut 2008
GERD: PATHOPHYSIOLOGY
Kahrilas, Clev Clin J Med 2003
GERD: DIAGNOSIS
Who What
Typical reflux symptoms without alarm signs Clinical history
Alarm signs Atypical reflux syndromes
Refractory GERD
Upper Endoscopy
Extra-esophageal syndromes Refractory GERD
24 hrs pH-impedance monitoring
Katz et al, Am J Gastroenterol 2013
GERD: DIAGNOSIS
Non erosive esophagitis
Barrett’s esophagus
Erosive esophagitis
Upper endoscopy
GERD: DIAGNOSIS
Esop
hage
al B
ody
(dis
tanc
e fr
om L
ES)
IMPE
DAN
CE
pH
Acid Reflux Weakly Acid Reflux
Reflux Reflux
Stomach
-5 cm from LES
Heartburn
24 hrs esophageal pH-impedance monitoring
GERD: DIAGNOSIS
24 hrs esophageal pH-impedance monitoring
Abnormal esophageal acid exposure
Reflux frequency
Reflux characteristics (acid/weakly acid/non acid; liquid/mixed)
Symptom association with reflux episodes
Symptom association probability (SAP) Symptom sensitivity index (SSI)
GERD: DIAGNOSIS OF EXTRAESOPHAGEAL SYNDROMES
GERD is a possibile co-factor in asthma, chronic cough,
laryngitis, pharyngitis
This association is rare if typical GERD symptoms are absent
Upper endoscopy is not useful in demonstrating the association
24 hrs esophageal pH-impedance monitoring
NEGATIVE
POSITIVE
direct the diagnosis toward non-GERD etiologies
evaluate temporal association between reflux and symptoms
Katz et al, Am J Gastroenterol 2013
GERD: THERAPY
Kahrilas, NEJM 2008
Dietary and lyfestyle recommandations Medical options
Protein pump inhibitors (PPI) 8 wk course of: omeprazole 20 mg/die pantoprazole 40 mg/die esomeprazole 40 mg/die lansoprazole 30 mg/die rabeprazole 20mg/die Histamine-receptors antagonists (H2RA) useful as a maintenance option Antiacids
Surgical options
Laparoscopic fundoplicatio Bariatric surgery
GERD AND LUNG
Strong epidemiological association between chronic lung
diseases and GERD
Evidence of benefit of GERD therapy on pulmonary function in
patients with chronic lung diseases
GERD AND LUNG
1 2 3 4
Foregut Anlage of the thyroid Anlage of the lungs Stomach
5 6 7
Anlage of the dorsal pancreas Midgut Hindgut
GERD AND LUNG
GERD AND LUNG
Emilsson et al, Gastroenterol Res Pract 2013
A proposed association between GERD and lung disease: possible ethiologies
GERD AND LUNG: MICROASPIRATION
Physiological and negligible during sleep in healthy subjects
Significant in consciousness alterations and pathological GERD
Gleeson et al, Chest 1997 Ravelli et al, Chest 2006
GERD AND LUNG: MICROASPIRATION
Chronic microaspiration
↑ TGF β
Lymphocytic bronchilitis obliterans
Pulmonary fibrosis
Perng et al, Chest 2007
The spectrum of lung disease due to Chronic Occult Aspiration
Cardasis et al, Ann Am Thorac Soc 2013
fibrosis granuloma giant cell
GERD AND LUNG: MICROASPIRATION
Proposed biomarkers
Emilsson et al, Gastroenterol Res Pract 2013
GERD AND LUNG: VAGAL REFLEX
Airway receptors
microaspiration
Esophageal receptors
Acidic pH High osmolality Pressure
GERD
Nucleus of the solitary tract
Vagal efferents
BRONCHOCONSTRICTION
Harding et al, Ann NY Acad Sci 2013
COUGH
Pulmonary autonomic system
TNFα, NGF and others
GERD AND LUNG: VAGAL REFLEX
Lang et al, Am J Physiol 2008 Wu et al, Chest 2000
GERD AND LUNG
Chronic lung diseases (COPD)
↑ abdominal pressure
↑ reflux episodes
Bronchoconstriction
↑ TLESR
Bronchodilator drugs
↓ LES tone
Chronic lung disease coud exacerbate GERD
Pulmonary hyperinflation
Diaphragm flattening
Harding et al, Ann NY Acad Sci 2013
GERD AND ASTHMA
Haveman et al, Gut 2008
Prevalence of reflux symptoms in patients with asthma
GERD AND ASTHMA
Haveman et al, Gut 2008
Prevalence of abnormal distal esophagus acid
exposure
Prevalence of esophagitis
GERD AND ASTHMA
Increased negative inspiratory intrathoracic pressure, bronchodilator therapy, chronic and acute airflow obstruction promote reflux
Microaspiration and vagally mediated bronchospasm are the proposed mechanisms by which reflux could trigger asthma
Esophageal acid exposure could enhance bronchial hyper-rensponsiveness rather than alter pulmonary function parameters
Temporal association between reflux and asthma has not been yet clarified.
Theodoropoulos et al, Allergy 1999
Harding et al, Ann NY Acad Sci 2013
Wu et al, Chest 2000
Haveman et al, Gut 2008
GERD AND ASTHMA
Morning peak expiratory flow and PPI
Chan et al, Arch Intern Med 2011
GERD AND ASTHMA
Author N patients
Treatment Asthma symptoms
Peak expiratory flow
Pulmonary function (FEV1)
Shimizu et al 30 Lansoprazole 30 mg for 8 wk Improved Improved Unchanged
Kiljander et al 107 Omeprazole 40 mg for 8 wk Improved Unchanged Improved
Kiljander et al 770 Esomeprazole 80 mg for 16 wk N/A Unchanged N/A
Stordal et al 38 Omeprazole 20 mg for 12 wk Unchanged N/A Unchanged
Boeree et al 36 Omeprazole 80 mg for 12 wk Unchanged Unchanged Unchanged
Littener et al 207 Lansoprazole 60 mg for 24 wk Unchanged Unchanged Unchanged
Jiang et al 30 Omeprazole 20 mg + domperidone 30 mg
Improved
Improved
Improved
Galmiche et al, Aliment Pharmacol Ther 2008
PPI therapy
Surgical therapy
Uncontrolled studies seem to show a benefit in relieving asthma symptoms Need for further evidence
GERD AND COPD
Prevalence of GERD symptoms
Prevalence of abnormal distal esophagus acid
exposure
30-53,6 57-62
Mokhlesi B, Chest 2001
Rogha M, J Gastrointest Liver Dis 2010
Casanova, Eur Respir J 2004
Kempainen, Chest 2007
GERD AND COPD
Typical GERD symptoms often absent The severity of GERD symptoms is higher in patients with more severe COPD
Hyperinflation is a factor risk for GERD
GERD is a factor risk for exacerbation Insufficient data on efficacy of PPI therapy
Kempainen, Chest 2007
Mokhlesi B, Chest 2001
Rascon-Aigiular, Chest 2006
Liang, Lung 2012
Sasaki, Ther Adv Respir Dis 2011
GERD AND IPF
In idiopatic pulmonary fibrosis a very high prevalence of asymptomatic GERD has been shown: abnormal distal reflux in 78% patients and proximal reflux in 33%
Pepsin documented in BALF of IPF patients with acute exacerbation
A history of laparoscopic fundoplication has found to be an indipendent predictor of longer survival
Gastro-esophageal reflux seem to be a contributor to the epithelial injury that leads to lung fibrosis and to the progression of the disease
Sweet, Ann Surg 2006
Lee, Eur Respir J 2012
Lee, Am J Respir Crit Care Med 2011
Allaix, J Gastrointest Surg 2013
GERD AND IPF
Lee, Am J Respir Crit Care Med 2011
GERD AND LUNG TRANSPLANT
Probable Potential
Acute rejection Aspergillus colonization of lower airways
CMV pneumonitis Aspiration
HLA mismatching CMV infection
Lymphocytic bronchitis/bronchiolitis Donor antigen-specific activity
Noncompliance with medications EBV reactivation
Primary graft disfunction Native lung disease
Gastroesophageal reflux
Older donor age
Pneumonia
Prolonged allograft ischemia
Recurrent infection other than CMV
GERD AND LUNG TRANSPLANT
Study No patients Abnormal distal reflux %
Increased nonacid reflux %
Hadjiliadis 2003 43 69.8
Cantu 2005 167 76
D’Ovidio 2006 50 at 3 mo 30 at 12 mo
26 50
Blondeau 2008 45 on PPI 18 off PPI
39 73
27 28
King 2009 61 65
Fisichella 2012 25 unilateral 30 bilateral 6 retransplant
24 63 100
GERD AND LUNG TRANSPLANT
upright recumbent total
Mea
n %
tim
e p
H <
4
P<0.05 P<0.05 P<0.05
ESOPHAGEAL ACID EXPOSURE IN LTx AND GERD
Di Stefano et al, SIGE 2011
GERD AND LUNG TRANSPLANT
upright recumbent total
Mea
n %
tim
e p
H <
4
P<0.05 P<0.05 P<0.05
ESOPHAGEAL ACID EXPOSURE IN LTx AND GERD
Di Stefano et al, SIGE 2011
GERD AND LUNG TRANSPLANT
Cantu et al, Ann Thorac Surg 2004
LUNG DISEASES AND GERD
No sufficient evidence for routine pulmonary function evaluation in GERD patients
No sufficient evidence for reflux screening and treatment (in absence of typical symptoms) in chronic lung diseases.
Further evidences are needed
Thank you for your attention