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

MURTALA ABDULLAHI AKANJI

Edited by Omotoso

Kayode

TABLE OF CONTENT
INTRODUCTION ASTHMA EFFICACY OF PPIs IN ASTHMA

CONCLUSION

INTRODUCTION
Proton pump inhibitors (PPIs) consist of a group of chemically 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)

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 cell where, at low pH, they are protonated, trapped, concentrated, and activated by conversion to the sulfenamide. (Richardson et al, 1998)

INTRO CONTD
The sulfenamide binds covalently to cysteine residues of the proton pump and irreversibly inhibits H+K+-ATPase and 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 pylori infection. (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)

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.

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.

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 by inhaling corticosteroids. Leukotriene antagonists are also useful although less effective. (Fanta, 2009)

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 when used in combination with SABA. (Self et al, 2009)

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 increased risk of severe symptoms. (Fanta, 2009)

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 to control asthma. (Anonymous, 1996) It is the passage of gastric contents through the gastric cardia into the oesophagus.

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 <4.0) to the distal oesophagus for more than 1.2 hours (cumulative time >5%) over a 24 hour period as. (Johnson and DeMeester, 1974; Johnsson et al, 1987)

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)

ASTHMA CONTD
Clinicians are advised to elucidate GERD as a potential trigger in asthma and when GERD is present, to consider treatment to improve asthma control. (Barnes, 1998)

The approaches to treat GERD:

H2 antagonists Proton pump inhibitors Cisapride Surgery including Nissen fundoplication and partial posterior hemi-fundoplication. (Coughlan et al, 2001)

EFFICACY OF PPIs IN ASTHMA

The reports of studies on the efficacy of PPIs in relieving asthma symptoms in asthmatic patients 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 and evening peak expiratory flow (PEF) rate. (Tsugeno et al, 2003)

EFFICACY CONTD
Kiljander et al (2005) reported esomeprazole at double the standard dose to improve PEF in nocturnal asthma. Yasuo (2006) reported that lansoprazole significantly improved PEF, asthma control questionnaire (ACQ) score and questionnaire for the diagnosis of reflux disease (QUEST) score.

EFFICACY CONTD
Esomeprazole (40mg) bid has no benefit to the primary treatment outcomes of subjective improvements in asthma function and secondary outcomes including pulmonary function, and nocturnal symptoms. (Woodruff, 2009)

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.

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.

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

EFFICACY CONTD
Overall, patients had a higher mean morning PEF rate after treatment with PPIs compared with placebo. Analyses of secondary outcomes (asthma symptoms score, Asthma Quality of Life Questionnaire score, evening PEF rate, and FEV1) showed no significant difference between PPIs and placebo. Chan et al (2011) concluded that the magnitude of improvement in morning PEF rate is insignificant in clinical practice.

CONCLUSION
As the association between asthma and GERD still remains conflicting, the efficacy of PPIs in asthmatics 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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