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THE EFFICACY OF PROTON PUMP
INHIBITORS FOR THE TREATMENTOF ASTHMA IN ADULTS
MURTALA ABDULLAHI AKANJI
Edited byOmotoso Kayode
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TABLE OF CONTENT
INTRODUCTION
ASTHMA
EFFICACY OF PPIs IN ASTHMA
CONCLUSION
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INTRODUCTION
Proton pump inhibitors (PPIs) consist of a group ofchemically related compounds called benzimidazole
derivatives.
Examples include omeprazole, lansoprazole,
pantoprazole, rabeprazole and esomeprazole
They inhibit the final common pathway of acid
production of gastric parietal cells. (Sachs et al, 1995)
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INTRO CONTD
Over the past 20 years, PPIs have revolutionized the
management of acid-related disorders in adults.(Sachs, 1997)
They act by non-competitively inhibiting H+K+-ATPase
(the proton pump), which is the final stage in gastric
acid secretion.
PPIs enter the canalicular lumen of the parietal cellwhere, at low pH, they are protonated, trapped,
concentrated, and activated by conversion to the
sulfenamide. (Richardson et al, 1998)
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INTRO CONTD
The sulfenamide binds covalently to cysteine residues of
the proton pump and irreversibly inhibits H+K+-ATPaseand gastric acid secretion. (Williams and Pounder, 1999)
Therapeutic uses of PPIs:
Gastroesophageal reflux disease (GERD). (Gibson et al, 2003)
Peptic ulcer. (Kato et al, 1996)
Helicobacter pyloriinfection. (Shcherbakov et al, 2001)
Cystic fibrosis (adjunct therapy). (Proesmans and Boeck, 2003)
Premedication for general anaesthesia. (Mikawa et al, 1995)
Stress ulceration (prevention). (Haizlip et al, 2005)
Barrets esophagus. (Weston et al, 1999)
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INTRO CONTD
Thus, the use of PPIs in asthma is based on the
hypothesis that GERD is a trigger for asthma.
(Sontang et al, 1990; Anonymous, 1996)
The question this review aims to answer is
whether PPIs are effective in relieving the
symptoms of asthma in patients with GERD.
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ASTHMA
Asthma is a chronic inflammatory disease of the
airways.
It is characterized by variable and recurring
symptoms, reversible airflow obstruction, and
bronchospasm.
Symptoms include wheezing, coughing, chest
tightness, and shortness of breath.
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ASTHMA CONTD
It is caused by a combination of genetic and
environmental factors. (Martinez, 2007)
Symptoms can be prevented by avoiding
triggers, such as allergens and irritants, and byinhaling corticosteroids.
Leukotriene antagonists are also useful
although less effective. (Fanta, 2009)
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ASTHMA CONTD
Drug treatment include the use of:
Short acting 2 agonists (SABA) e.g.salbutamol.
Anticholinergic drugs e.g. Ipratropium
bromide provide addition benefit whenused in combination with SABA. (Selfet al,
2009)
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ASTHMA CONTD
Non-selective adrenergic agonist e.g.epinephrine. (Rodrigo and Nannini, 2006)
Although not recommended due to their cardiac
stimulating potential.
Glucocorticoids.
Long acting 2 agonist (LABA) have at least a
12-hour effect. They are however not to be
used without a steroid due to an increasedrisk of severe symptoms. (Fanta, 2009)
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ASTHMA CONTD
Gastro-oesophageal reflux occurs frequently
in adults and children with asthma. (Sontag et
al, 1990; Tucci et al, 1993; Kirjander, 2003)
GERD is reported to be a trigger for difficult tocontrol asthma. (Anonymous, 1996)
It is the passage of gastric contents through
the gastric cardia into the oesophagus.
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ASTHMA CONTD
A reflux can be a physiological event occuring
mainly after meals in healthy people.
Abnormal reflux is defined as significant acid
exposure (pH 5%) over a 24 hour period as. (Johnson and
DeMeester, 1974; Johnsson et al, 1987)
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ASTHMA CONTD Mechanisms by which GERD may trigger
asthma include: Microaspiration of acid. (Mays, 1976; Tuchman et al, 1984)
Direct acid stimulation of the oesophagus. (Canning and
Mazzone, 2003)
Stimulation of vagal nerves which heightens bronchial
responsiveness to extrinsic allergens. (Mansfield, 1989;
Altschuler, 2001)
Airway pH deviation-induced inflammation. (Ricciardolo,
2004)
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ASTHMA CONTD
Clinicians are advised to elucidate GERD as a
potential trigger in asthma and when GERD ispresent, to consider treatment to improve asthmacontrol. (Barnes, 1998)
The approaches to treat GERD: H2 antagonists
Proton pump inhibitors
Cisapride Surgery including Nissen fundoplication and
partial posterior hemi-fundoplication. (Coughlanet al, 2001)
EFFICACY OF PPI IN ASTHMA
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EFFICACY OF PPIs IN ASTHMA
The reports of studies on the efficacy of PPIs
in relieving asthma symptoms in asthmaticpatients with concomitant GERD are
conflicting:
The PPI, omeprazole improves asthma symptoms.(Ford et al, 1994; Meier et al, 1994; Harding et al,
1996; Teichtahl et al, 1996)
Rabprazole (20mg) bid improves morning andevening peak expiratory flow (PEF) rate. (Tsugeno
et al, 2003)
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EFFICACY CONTD
Kiljander et al(2005) reported esomeprazole
at double the standard dose to improve PEF innocturnal asthma.
Yasuo (2006) reported that lansoprazole
significantly improved PEF, asthma control
questionnaire (ACQ) score and questionnaire
for the diagnosis of reflux disease (QUEST)
score.
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EFFICACY CONTD
Esomeprazole (40mg) bid has no benefit to
the primary treatment outcomes of subjectiveimprovements in asthma function and
secondary outcomes including pulmonary
function, and nocturnal symptoms. (Woodruff,2009)
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EFFICACY CONTD
Kirjander, 2003:
It appear that PPI treatment may improve
nocturnal asthma symptoms in patients who also
have GERD.
Both daytime asthmatic symptoms and pulmonary
function seem to improve in some patients with
PPI treatment.
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EFFICACY CONTD
There is evidence that more severe GERD might
predict a more favorable asthma outcome with
PPI therapy.
Kirjander therefore suggested that for effective
management of GERD-related asthma, PPIs should
be used at a dose double that of the standard
dose for a minimum of 2 to 3 months.
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EFFICACY CONTD Chan et al(2011) conducted a meta-analysis study using
the following endpoints:
Main endpoint Morning PEF rate
20 objective endpoints:
Evening PEF rate
Forced expiratory volume in 1 sec (FEV1)
20 subjective endpoints:
Asthma symptom score measure
Asthma quality of life questionnaire score
measure
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EFFICACY CONTD Overall, patients had a higher mean morning PEF
rate after treatmentwith PPIs compared withplacebo.
Analyses of secondaryoutcomes (asthmasymptoms score, Asthma Quality of Life
Questionnaire
score, evening PEF rate, and FEV1)
showed no significant difference between PPIsand placebo.
Chan etal (2011) concluded that the magnitudeof improvementin morning PEF rate isinsignificant in clinical practice.
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CONCLUSION
As the association between asthma and GERD
still remains conflicting, the efficacy of PPIs inasthmatics with concomitant GERD remains
unresolved.
More studies therefore are needed to assess
the clinical importance of PPIs in relieving
asthma symptoms.
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THANK YOU.