Sunny Jabbal

• MB ChB; MRCP(UK); MD
• Consultant at NHS Borders

Capsule summary: We demonstrate that extra-fine particles are not associated with an appreciably higher exhaled fraction, hence explaining their efficacy profile in asthma.

We have previously shown in a cohort of patients with asthma that impulse oscillometry (IOS) and spirometry are equally useful in predicting asthma control as assessed by prescriptions of oral corticosteroid and inhaled albuterol using health informatics.1 These were patients referred from primary care for screening into clinical trials. We wanted...

Background: Tiotropium is a long acting antimuscarinic (LAMA), licenced as triple therapy with inhaled corticosteroid and long acting beta-agonist (ICS/LABA). There may be a synergistic benefit between LAMA and LABA as a consequence of receptor cross-talk, which in turn could modify beta-2 receptor down-regulation and associated tolerance induced...

Background: Beta-blockers remain underused in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Aim: We compared how different inhaled therapies affect tolerability of bisoprolol and carvedilol in moderate to severe COPD. Design: A randomized, open label, cross-over study. Methods: We compared the cardiop...

Background Airway hyperresponsiveness (AHR) and eosinophilia are hallmarks of persistent asthma. Objective We investigated whether eosinophil depletion with benralizumab (Benra) might attenuate indirect mannitol AHR in severe uncontrolled asthma using a pragmatic open label design. Methods After a 4-week run-in period on usual ICS/LABA (baseline)...

Background Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate. Methods We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hos...

Despite the success of vaccines and selected repurposed treatments, COVID-19 is likely to remain a global health problem and further chemotherapeutics are required. Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials without characterisation of Pharmacokinetics (PK)/Pharmacodynamics (PD) including safety in COVID-19. One such drug...

Background Smoking worsens underlying asthma inflammation and also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with worse control. Objectives We investigated the effects on small airways of adding long acting beta‐agonist (LABA) alone or with long acting muscar...

Background Beta-blockers (BB) are underused in COPD despite evidence for reducing mortality from cardiovascular comorbidities. Beta-1 selective antagonists such as bisoprolol (BIS) may cause bronchoconstriction due to dose related beta-2 blockade. Celiprolol (CEL) is a beta-1 selective antagonist which also exhibits partial beta-2 agonist activity....

Background Patients with asthma who smoke are difficult to manage and are usually excluded from clinical trials. Smoking not only worsens underlying asthma inflammation and airway hyper-responsiveness but also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with wor...

Background The forced oscillation technique (FOT) measures respiratory impedance during normal tidal breathing and requires minimal patient cooperation. Objective To compare IOS and AOS devices in patients with asthma and COPD. Methods We compared two different FOT devices, namely impulse oscillometry using a loudspeaker (IOS: Jaeger Masterscreen...

Background: Extra-fine particle formulations of inhaled corticosteroid (ICS) are associated with improved lung delivery. Objectives: A pragmatic study to assess patient reported outcomes after switching from fine to extra-fine particle ICS in persistent asthma. Methods: 24 patients (Mean age 48 year, FEV1 84%, ACQ 1.67) received 4 weeks run-in...

Aims To demonstrate the noninferiority of extrafine beclomethasone/formoterol fumarate (BDP/FF) dry powder inhaler (DPI) vs. extrafine BDP/FF pressurized metered dose inhaler (pMDI; Foster® 100/6 μg NEXThaler and pMDI, respectively) in the onset of reliever effect after methacholine induced bronchospasm in asthmatic patients, evaluated in terms of...

A single inhaler containing inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA) is a more convenient way of delivering triple therapy in patients with COPD. Single triple therapy has been shown to be superior at reducing exacerbations and improving quality of life compared to LABA/LAMA, especially i...

Impulse oscillometry (IOS) is the most commonly used type of forced oscillation technique in clinical practice, although relatively little is known about its application in COPD. Resistance at 20 Hz (R20) is unrelated to COPD severity and does not improve with bronchodilatation or bronchoconstriction, inferring a lack of large airway involvement in...

Little is known about impulse oscillometry (IOS) in COPD. IOS is an effort independent measure of lung resistance and reactance (compliance). We assessed how frequency dependence of resistance (R) and reactance (X) changed in response to bronchoconstriction with carvedilol followed by long acting beta-agonist (LABA) withdrawal. N = 12 patients with...

We investigated if serial domiciliary measures of spirometry were sensitive at detecting subtle effects of beta-2 blockade associated with bisoprolol. This was a sub-study of NCT01656005 where domiciliary diary data were available on n=17 patients with GOLD B/C COPD comprising domiciliary FEV1,(am/pm), heart rate, oxygen saturation, salbutamol use,...

Control based asthma management results in improved asthma outcomes. The Asthma Control Questionnaire (ACQ-6), is a widely used and well validated metric which strongly predicts future exacerbations.¹ It demarcates between controlled (C), partially controlled (P), and uncontrolled (U), based on cut point scores of <0.75, 0.75<1.5, and ≥1.5 respecti...

Blood eosinophil counts which were once regarded as normal, have become of increasing interest in the era of Interluekin-5 (IL-5) asthma treatment. Blood eosinophils as low as 150 cells/μL have been suggested as treatment cut-offs for eosinophil depleting therapies such as mepolizumab [1], whilst a value of 300 cells/μL has been deemed a more pragm...

We investigated if serial domiciliary measures of spirometry were sensitive at detecting subtle effects of beta-2 blockade associated with bisoprolol in (n = 17) patients with COPD. After a two-week run in on inhaled corticosteroid (ICS) and long acting beta-2 agonist (LABA): beclometasone/formoterol 100/6 µg, patients’ started additional a long ac...

Background Inhaled corticosteroid (ICS) titration in asthma is primarily based on symptoms and pulmonary function. ICSs may not be increased on this basis despite residual airway inflammation. Objective To compare the dose-response relationships of ICSs on measures of pulmonary function, symptoms, and inflammation in patients with persistent ast...

Background Long acting muscarinic antagonists (LAMA) such as tiotropium (TIO) reduce asthma exacerbations in patients receiving inhaled corticosteroids and long-acting beta-agonists (ICS/LABA). However the mechanism for this protective action of LAMA remains unclear. Objectives To evaluate the response to indacaterol (IND) either alone in combinat...

GINA guidelines state asthma patients should be on the lowest treatment step to achieve control. In clinical practice more often patients are stepped up to ICS/LABA than stepped down. We hypothesise that LABA withdrawal may be safely done in controlled patients.Methods:We evaluated 58 stable, step 3 asthma patients from primary care. Spirometry, Im...

Purpose: We evaluated whether Gly16Arg beta2-receptor genotype relates to impulse oscillometry (IOS) in a real-life clinic setting. Methods: Patients with persistent asthma taking inhaled corticosteroid ± long-acting beta-agonist (ICS ± LABA) were evaluated. We compared genotype groups comprising either no Arg copies (i.e. GlyGly) versus one or tw...