Papers by Jaymin Morjaria
Therapeutic Advances in Chronic Disease, 2014
Opiates have been used for cough suppression for centuries. It is unclear whether this antitussiv... more Opiates have been used for cough suppression for centuries. It is unclear whether this antitussive action is due to their known sedative effects. We aimed to assess correlation between cough suppression and opiate usage. We performed a post hoc analysis of two published trials with three opioids. In study one, patients with chronic cough were treated with 4 weeks of modified release morphine sulphate (5 mg twice daily) or placebo in a double-blinded placebo-controlled fashion. Cough suppression was assessed subjectively by the Leicester Cough Questionnaire and objectively by citric acid aerosol (CAA) induced cough challenge. In study 2, normal volunteers were given single doses of placebo, codeine 30 mg or dextromethorphan 50 mg and cough suppression assessed using the CAA-induced cough challenge. Sedation was contemporaneously assessed by direct questioning. There were 14 episodes of patient-reported sedation; 2 with modified release morphine sulphate, 9 with codeine and 3 with dextromethorphan. There was no correlation between change in the Leicester Cough Questionnaire or the CAA-induced cough challenge and reported sedation. This observational study suggests that sedation is unlikely to underlie the antitussive properties of these opioids. Eliciting the mechanism of these medications in cough may be a target for future tailored drug development.
Cigarette smoking is a tough addiction to break. Therefore, im-proved approaches to smoking cessa... more Cigarette smoking is a tough addiction to break. Therefore, im-proved approaches to smoking cessation are necessary. The electronic cigarette may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption. To date there is no formal demonstration supporting the efficacy of these devices in smoking cessation and/or smoking reduction studies.
Journal of Allergy and Clinical Immunology, 2015
Electronic cigarettes (e-cigs) are marketed as safer alternatives to tobacco cigarettes and have ... more Electronic cigarettes (e-cigs) are marketed as safer alternatives to tobacco cigarettes and have shown to reduce their consumption. Here we report for the first time the effects of e-cigs on subjective and objective asthma parameters as well as tolerability in asthmatic smokers who quit or reduced their tobacco consumption by switching to these products. We retrospectively reviewed changes in spirometry data, airway hyper-responsiveness (AHR), asthma exacerbations and subjective asthma control in smoking asthmatics who switched to regular e-cig use. Measurements were taken prior to switching (baseline) and at two consecutive visits (Follow-up/1 at 6 (±1 ) and Follow-up/2 at 12 (±2) months). Eighteen smoking asthmatics (10 single users, eight dual users) were identified. Overall there were significant improvements in spirometry data, asthma control and AHR. These positive outcomes were noted in single and dual users. Reduction in exacerbation rates was reported, but was not significant. No severe adverse events were noted. . J. Environ. Res. Public Health 2014, 11 4966 This small retrospective study indicates that regular use of e-cigs to substitute smoking is associated with objective and subjective improvements in asthma outcomes.
Pulmonary Pharmacology & Therapeutics, 2014
Background: Regular treatment with inhaled corticosteroids (ICS) is known to reduce airway hyperr... more Background: Regular treatment with inhaled corticosteroids (ICS) is known to reduce airway hyperresponsiveness (AHR) to adenosine 5 0 -monophosphate (AMP) in asthma even after a single dose of fluticasone propionate (FP). Aim: To determine whether this rapid protective effect of a single dose of FP is also present in COPD. Methods: 23 mild asthmatic and 24 COPD subjects with documented AHR to both AMP and methacholine took part in a randomized, double-blind, placebo-controlled, crossover study to measure AHR to inhaled AMP and methacholine 2 h after either 1000 mg FP or matched placebo. Results: In subjects with asthma, 1000 mg FP in a single dose significantly attenuated the constrictor response to AMP, geometric mean (range) PC20AMP values increasing from a 19.2 (1.3e116.3) to 81.5 (9.6 e1600.0) (p < 0.001; post-placebo vs post-FP) mg/ml. Change in the airways response to inhaled AMP after FP was well within test variability in patients with COPD, with PC20AMP values 59.6 (11.3e183.9) and 76.3 (21.0e445.3) (p ¼ 0.022; post-placebo vs post-FP) mg/ml. Additionally, FP failed to significantly attenuate the bronchial response to methacholine in both asthma and COPD subjects. A change in doubling dilution, between placebo and following a single dose of FP, in AMP had a better sensitivity and specificity of 95.8% and 65.2%, compared to methacholine of 79.2% and 43.5% respectively in delineating between COPD and asthma.
Internal and Emergency Medicine, 2013
Electronic cigarettes (e-Cigarette) are battery-operated devices designed to vaporise nicotine th... more Electronic cigarettes (e-Cigarette) are battery-operated devices designed to vaporise nicotine that may aid smokers to quit or reduce their cigarette consumption. Research on e-Cigarettes is urgently needed to ensure that the decisions of regulators, healthcare providers and consumers are evidence based. Here we assessed long-term effectiveness and tolerability of e-Cigarette used in a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;naturalistic&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; setting. This prospective observational study evaluated smoking reduction/abstinence in smokers not intending to quit using an e-Cigarette (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Categoria&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;; Arbi Group, Italy). After an intervention phase of 6 months, during which e-Cigarette use was provided on a regular basis, cigarettes per day (cig/day) and exhaled carbon monoxide (eCO) levels were followed up in an observation phase at 18 and 24 months. Efficacy measures included: (a) ≥50% reduction in the number of cig/day from baseline, defined as self-reported reduction in the number of cig/day (≥50%) compared to baseline; (b) ≥80% reduction in the number of cig/day from baseline, defined as self-reported reduction in the number of cig/day (≥80%) compared to baseline; (c) abstinence from smoking, defined as complete self-reported abstinence from tobacco smoking (together with an eCO concentration of ≤10 ppm). Smoking reduction and abstinence rates were computed, and adverse events reviewed. Of the 40 subjects, 17 were lost to follow-up at 24 months. A &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% reduction in the number of cig/day at 24 months was shown in 11/40 (27.5%) participants with a median of 24 cig/day use at baseline decreasing significantly to 4 cig/day (p = 0.003). Smoking abstinence was reported in 5/40 (12.5%) participants while combined &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% reduction and smoking abstinence was observed in 16/40 (40%) participants at 24 months. Five subjects stopped e-Cigarette use (and stayed quit), three relapsed back to tobacco smoking and four upgraded to more performing products by 24 months. Only some mouth irritation, throat irritation, and dry cough were reported. Withdrawal symptoms were uncommon. Long-term e-Cigarette use can substantially decrease cigarette consumption in smokers not willing to quit and is well tolerated. ( http://ClinicalTrials.govnumberNCT01195597 ).
BMC Public Health, 2014
Background: Electronic cigarettes (e-Cigs) are an attractive long-term alternative nicotine sourc... more Background: Electronic cigarettes (e-Cigs) are an attractive long-term alternative nicotine source to conventional cigarettes. Although they may assist smokers to remain abstinent during their quit attempt, studies using first generation e-Cigs report low success rates. Second generation devices (personal vaporisers -PVs) may result in much higher quit rates, but their efficacy and safety in smoking cessation and/or reduction in clinical trials is unreported.
Thorax, 2008
Tumour necrosis factor alpha (TNFalpha) is a cytokine recognised as a therapeutic target in chron... more Tumour necrosis factor alpha (TNFalpha) is a cytokine recognised as a therapeutic target in chronic inflammatory diseases. A randomised, double blind, placebo controlled parallel group trial is reported of etanercept (an IgG1-TNF p75 receptor fusion protein), administered once weekly for 12 weeks in 39 patients with severe corticosteroid refractory asthma. Efficacy was measured by change from the pretreatment baseline in Asthma Related Quality of Life (AQLQ) and Asthma Control (ACQ) Questionnaire scores (the primary endpoints), lung function, peak expiratory flow (PEF) and bronchial hyperresponsiveness (BHR). Sputum and serum inflammatory cells and cytokines, serum albumin and C reactive protein (CRP) as biomarkers of inflammation were also assessed. There was a small but significant difference in reduction of ACQ scores between treatment and placebo (-1.11 (95% CI -1.56 to -0.75) and -0.52 (95% CI -0.97 to -0.07), respectively, p = 0.037). There was no significant difference in improvements in AQLQ scores, lung function, PEF, BHR or exacerbation rates between the groups. Minor adverse events, including injection site pain and skin rashes, were more frequent with etanercept. There was a significant reduction in sputum macrophages and CRP, and increases in serum TNFalpha and albumin following treatment, but not in other laboratory parameters. Etanercept therapy over 12 weeks demonstrated only a small but significant improvement in asthma control and systemic inflammation, as measured by serum albumin and CRP. Larger randomised, placebo controlled trials are required to clarify the role of TNFalpha antagonism in subjects with severe refractory asthma.
Case Reports, 2013
Herniation of the lung is uncommon and occurs due to protrusion of the lung beyond the confines o... more Herniation of the lung is uncommon and occurs due to protrusion of the lung beyond the confines of the thoracic cavity through an abnormal opening in the chest wall. Any condition associated with raised intrathoracic pressure or that which weakens the thoracic wall may result in lung herniation. We present a case of spontaneous lung herniation which was managed successfully by minimally invasive thoracic surgery.
Therapeutic Advances in Chronic Disease, 2014
Pneumothoraces may be due a variety of aetiologies. Here we present two different cases: one with... more Pneumothoraces may be due a variety of aetiologies. Here we present two different cases: one with a unilateral pneumothorax due an iatrogenic medical procedure and another of idiopathic spontaneous bilateral nature. Although both cases were initially managed conservatively, the latter case required surgical intervention. We also conduct a literature review of the aetiology and management of pneumothoraces.
Therapeutic Advances in Chronic Disease, 2010
Therapeutic Advances in Chronic Disease, 2011
Asthma usually presents with symptoms of wheeze, dyspnoea and cough. However, clinicians should b... more Asthma usually presents with symptoms of wheeze, dyspnoea and cough. However, clinicians should be aware of atypical presentation of this disorder when cough is the main or only symptom in conditions such as cough-variant asthma, nonasthmatic eosinophilic bronchitis and atopic cough. Early diagnosis and treatment of these conditions with inhaled corticosteroids improves symptoms in the majority of patients. Up to 10% of patients with asthma remain poorly controlled in spite of optimal standard therapy. These patients have been encompassed under the term &amp;amp;amp;amp;amp;amp;#39;treatment-refractory asthma&amp;amp;amp;amp;amp;amp;#39; (TRA), have the greatest morbidity and are responsible for more than 50% of healthcare costs. In this review we discuss investigations, management and pathophysiology of the various phenotypes of atypical presentations of asthma as well as novel biological agents licensed and those that have been reported in clinical trials in terms of their efficacy and safety in TRA.
European Respiratory Journal
Diaphragmatic hernias that are diagnosed in adulthood may be traumatic or congenital in nature. T... more Diaphragmatic hernias that are diagnosed in adulthood may be traumatic or congenital in nature. Therefore, respiratory specialists need to be aware of the presentation of patients with these conditions. In this report, we describe a case series of patients with congenital and traumatic diaphragmatic hernias and highlight a varied range of their presentations. Abnormalities were noted in the thorax on the chest radiographs, but it was unclear as to the nature of the anomaly. The findings on thoracic ultrasound conducted by a pulmonologist helped to direct appropriate investigations avoiding unnecessary interventions. Instead of pleural effusions, consolidation or collapse, thoracic computed tomography demonstrated diaphragmatic hernias which were managed either conservatively or by surgery. There is increasing evidence that pulmonary specialists should be trained in thoracic ultrasonography to identify pleural pathology as well as safely conducting pleural-based interventions.
Internal and Emergency Medicine, 2011
Patients with chronic obstructive pulmonary disease (COPD) are prone to clinical exacerbations th... more Patients with chronic obstructive pulmonary disease (COPD) are prone to clinical exacerbations that are associated with increased airway inflammation, a potent pro-thrombotic stimulus. Limited information is available on the mechanisms underlying the putative alterations of the endothelial-coagulative system during acute exacerbations. The aim was to investigate whether the activation of the endothelial-coagulative system occurs in association with the acute inflammatory response of COPD exacerbation. We monitored the blood levels of surrogate markers of inflammation: interleukin-6 (IL-6); endothelium damage: von Willebrand&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s factor (vWF); clotting activation: D-dimer (D-D), and prothrombin fragment 1+2 (F1+2); fibrinolytic response: plasminogen activator inhibitor 1 (PAI-1), in COPD subjects, during hospital admission and after clinical resolution. In 30 COPD subjects, IL-6, vWF, D-D and F1+2 levels were elevated during exacerbation and decreased significantly at clinical stability (IL-6, p = 0.005; vWF, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; D-D, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; F1+2, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). PAI-1 levels did not change at exacerbation compared to clinically stable situations. Positive correlations were observed between several of the markers measured. Elevation of IL-6, vWF, D-D and F1+2 levels during COPD exacerbations implies a strict association between acute inflammation, endothelial activation and clotting initiation. This was not associated with a change in PAI-1, implying an increase in the fibrinolytic response to inflammation. The pro-thrombotic nature of COPD exacerbations sustained by enhanced clotting activation appears to be mitigated by excessive fibrinolysis.
Therapeutic Advances in Respiratory Disease, 2015
International Journal of Chronic Obstructive Pulmonary Disease, 2014
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized... more Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. Bronchodilator therapy is the cornerstone in COPD treatment. Bronchodilation in COPD is mainly achieved via administration of long- and ultralong-acting β2-agonists and with long-acting muscarinic antagonists. New combinations of bronchodilators with dual-acting muscarinic antagonist and β2-agonist properties have been licensed, and others are currently being developed with the aim of achieving once-daily dosing, and therefore may improve the likelihood of treatment compliance. These combination bronchodilators include glycopyrronium bromide/indacaterol maleate, umeclidinium (UMEC) bromide/vilanterol trifenatate (VI), aclidinium bromide/formoterol and tiotropium bromide/olodaterol (Boehringer Ingelheim, Germany). This review will focus mainly on studies and clinical trials involving the novel fixed-dose combination of UMEC/VI at doses of 125/25 μg and 62.5/25 μg in patients with COPD. Data from large clinical trials involving more than 4,500 COPD patients indicate that UMEC/VI is an effective once-daily treatment in COPD with improved pulmonary function. Future studies assessing the impact of this combination on exacerbations, delay in disease progression, and health status in patients with COPD are warranted.
Current Allergy and Asthma Reports, 2011
Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequen... more Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite treatment with high-dose steroid and other currently available therapies. These patients are also at risk of developing steroid-related side effects, and their severe, unrelenting symptoms have a huge impact on health care resources due to frequent hospital admissions and requirement for intensive medication use. Consequently, a compelling need exists for more effective and safer pharmacotherapies to help them achieve adequate disease control. Recent novel therapies for severe asthma are now emerging, some of the most promising of which are monoclonal antibodies. Monoclonal antibodies represent a form of immunotherapy used in a wide variety of therapeutic roles. The spectrum of disease states in which monoclonal antibodies have been approved for therapeutic use now includes respiratory and allergic diseases. At present, only one drug is licensed for allergic asthmatics with severe disease, omalizumab. We review some of the currently available biologics that are approved or under investigation for use in severe asthma. Some have shown to be useful in specifically targeted subpopulations of patients with severe asthma, whereas other have proven to be unsafe and/or unsuccessful. Despite these developments, more effort should be devoted to identifying new molecular targets, testing innovative approaches, and establishing the best use of what is available. Regarding this latter point, identifying individual characteristics that predict successful responses to these treatments is highly desirable.
International Journal of Chronic Obstructive Pulmonary Disease, 2015
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. The cor... more Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. The cornerstone of pharmacological treatment for COPD is bronchodilation. Inhaled glycopyrronium bromide is a long-acting muscarinic antagonist developed as a maintenance treatment for patients with COPD. Phase III trials have shown that glycopyrronium produces rapid and sustained bronchodilation with an efficacy similar to tiotropium and is well tolerated, with a low incidence of muscarinic side effects in patients with moderate to severe COPD. A combination of glycopyrronium bromide with indacaterol maleate (QVA149) has recently been approved as a once-daily maintenance therapy in adult patients with COPD. Phase III trials (the IGNITE program) with QVA149 have demonstrated significant improvements in lung function versus placebo, glycopyrronium, and tiotropium in patients with moderate to severe COPD, with no safety concerns of note. Hence QVA149 is a safe treatment option for moderate to severe COPD patients in whom long-acting muscarinic antagonist monotherapy is inadequate.
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Papers by Jaymin Morjaria