THE EFFICACY OF PROTON PUMP INHIBITORS FOR THE TREATMENT OF ASTHMA IN ADULTS

7/30/2019 THE EFFICACY OF PROTON PUMP INHIBITORS FOR THE TREATMENT OF ASTHMA IN ADULTS

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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.

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THE EFFICACY OF PROTON PUMP INHIBITORS FOR THE TREATMENT OF ASTHMA IN ADULTS