Asthma and obstructive sleep apnoea in the UK and the UAE : clinical association, pathophysiological inter-relation and impact of therapy

Abstract

Introduction: Asthma and Obstructive Sleep Apnoea (OSA) are highly prevalent respiratory disorders and frequently coexist. Although both asthma and OSA are common, the overlap between the two disorders seems to be more that would be expected by chance alone. This observation suggests there may be some links, possibly causative, between the two disorders. In fact, there is a need for more data regarding clinical pharmacists’ intervention on drug therapy improvement especially with respiratory and GOR diseases. In this regard, the importance of clinical pharmacy-based services that improve medication adherence and dosage regimen in patients with respiratory diseases and GOR is not negligible. Thus, an additional studies that evaluate the effect of such services on certain clinical and pharmaco-therapeutic aspects of asthma, OSA and GOR treatments for larger patient samples are required. Aims: To examine some proposed clinical and pathophysiological mechanisms (Reflux, lung pathophysiology and cough) between asthma and OSA and to investigate the therapeutic impact of CPAP on the pharmacotherapy of asthma (asthma medications) and GOR (Proton Pump Inhibitors (PPIs) in an international collaboration involving centres in the UK and UAE. Methodology: Patients were recruited directly from designated consultant clinics at Newcastle upon Tyne hospitals, UK. Data from four groups of participants (n= 42): patients with OSA and asthma (n=10), asthma alone (n=10), OSA alone (n=10) and control subjects (n=12) were studied. All subjects at recruitment underwent detailed pulmonary function tests (PFTs) (FEV1, FVC, FEV1/VC, FEF50, FEF 25-75, SGaw, SGaw ratio), completed questionnaires about symptoms of gastro-oesophageal reflux, sleepiness and cough; Reflux Symptoms Index (RSI score), Epworth Sleepiness Scale (ESS) and Leicester-Cough and provided a sample of saliva. Subjects then underwent one hour CPAP as intervention. PFTs were repeated for all subjects after 1-hour CPAP. For patients with OSA, with or without asthma, there was a one-month period of treatment with home CPAP after which all PFTs, questionnaires and saliva collection were repeated. Medications for all groups were reviewed and recorded at baseline and after 1- month of CPAP therapy for statistical analysis and interpretation. In a parallel study, another independent cross-sectional observational study of 312 patients was performed at Rashid Hospital, Dubai, UAE in the time period between September 2014 to September 2016 to investigate OSA associated comorbidities (including asthma) using Polysomnography and consultants diagnosis. Results: The RSI score discriminated reflux symptoms among subject groups at baseline; with pathophysiological levels of symptoms found in 0% of Controls, 40% of asthmatics, 60% of OSA patients and 80% of patients when asthma was overlapped with OSA. Salivary pepsin showed no statistical significance between all groups at baseline (P= 0.30). The asthma + OSA group had higher levels of pepsin than the asthma group (P= 0.01). Cough assessment showed a significant difference for all groups at baseline (P= 0.01) and between all asthma groups compared to controls (P=0.00). No significant difference was found in salivary pepsin concentration for all asthma patients compared to controls at baseline (P= 0.74). CPAP showed no measurable effect on airways function (P> 0.05). Reflux measured by salivary pepsin concentration (Pepsin ≥ 25ng/ml) and RSI (RSI ≥13) significantly reduced after a month CPAP treatment in patients with OSA (P= 0.05), (P= 0.04) respectively and in asthma overlapped OSA (P=0.00), (P= 0.00) respectively. ESS showed a trend for improvement following one month CPAP in OSA (P= 0.07) and asthma + OSA (P= 0.07) patients. In a novel finding, around 23% (n= 10) of the total number of participants (n=42) were on different PPI medications (Omeprazole and Lansoprazole) at baseline. The impact of CPAP on PPI medications was significant after 1-month therapy. All OSA patients who were taking PPIs discontinued these medications after 1-month CPAP, associated with the symptomatic resolution of their reflux (p= 0.00). On the other hand, CPAP showed no effect on asthma medications after 1-month treatment. The UAE study showed a statistical association between OSA and obesity (P= 0.00), diabetes (P= 0.04) and hypertension (P=0.00) and a non-significant association with asthma (P= 0.49). Conclusion: This pilot work showed that coordinated studies of airways physiology, sleep and assessment of reflux was possible in this patient setting and that OSA, asthma and overlap is an international healthcare problem. This study, implied a pathophysiological plausible association between reflux and dysregulated sleep physiology and that CPAP may modulate reflux and microaspiration. The significant impact of CPAP on GORD pharmacotherapy was confirmed in VII this study. PPIs were discontinued after 1-month CPAP in all OSA patients as a result of GORD symptoms resolution. If confirmed, these novel findings could be of translational significance in a patient population that is international, large and expanding and where new therapeutic strategies are a healthcare priority