Objectives. To assess the induced sputum substance P (ISSP) levels in children having difficult-to-treat asthma (DA) with and without gastroesophageal reflux (GER). We aimed also to evaluate the association of GER with childhood DA, relationship of GER severity with childhood asthma control test (C-ACT), FEV1, peak expiratory flow (PEF) variability, and ISSP. Finally, we tried to evaluate esomeprazole treatment effect on C-ACT and FEV1 in children with DA. Methods. Spirometry, C-ACT, upper gastrointestinal endoscopy, and ISSP measurement were done for children with DA compared to healthy controls. Results. ISSP was high in DA with higher levels in the group having associated GER. In the latter group, ISSP and C-ACT improved significantly after esomeprazole treatment while FEV1 and PEF variability did not improve. Reflux severity was positively correlated with ISSP and negatively correlated with FEV1. Conclusions. GER was found in 49% of our patients with childhood DA. Very high ISSP levels in children with DA may be used as a marker for presence of GERD. Esomeprazole therapy improved asthma symptoms but did not improve lung function. 1. Introduction Asthma is a common chronic complex inflammatory airway disorder characterized by variable degrees of recurring symptoms of airflow obstruction and bronchial hyperresponsiveness . Although the majority of asthma patients can obtain the targeted level of control, some patients will not achieve control even with the best therapy . Patients who do not reach an acceptable level of control with the use of reliever medication plus two or more controllers can be considered to have difficult-to-treat asthma . The association between asthma and gastrooesophageal reflux (GER) has been debated for decades when Sir William Osler first observed the association between worsening asthma and distended stomach in 1892 . The prevalence of symptoms of GER among individuals with asthma is substantially higher than in normal population and similarly the prevalence of asthma in individuals with GER is also higher than in controls . Gastroesophageal reflux (GER) may cause chronic respiratory disease by vagal response and tracheal aspiration of gastric contents . Aspiration of gastric contents changes pulmonary resistance and causes reactive airway obstruction . Gastrooesophageal reflux may contribute to airway inflammatory events, possibly by sensory nerve stimulation and the subsequent release of tachykinins into the airway . The tachykinins as substance P (SP) and neurokinin A are the neuropeptides most
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