Imperial College London

Dr Melissa Wickremasinghe

Faculty of MedicineNational Heart & Lung Institute

Honorary Clinical Senior Lecturer







Praed StreetSt Mary's Campus





Publication Type

13 results found

Saketkoo LA, Mittoo S, Frankel S, LeSage D, Sarver C, Phillips K, Strand V, Matteson ELet al., 2014, Reconciling Healthcare Professional and Patient Perspectives in the Development of Disease Activity and Response Criteria in Connective Tissue Disease–related Interstitial Lung Diseases, The Journal of Rheumatology, Vol: 41, Pages: 792-798, ISSN: 0315-162X

<jats:p>Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.</jats:p>

Journal article

Keir GJ, Maher TM, Ming D, Abdullah R, de Lauretis A, Wickremasinghe M, Nicholson AG, Hansell DM, Wells AU, Renzoni EAet al., 2014, Rituximab in severe, treatment-refractory interstitial lung disease, RESPIROLOGY, Vol: 19, Pages: 353-359, ISSN: 1323-7799

Journal article

Saketkoo LA, Mittoo S, Huscher D, Khanna D, Dellaripa PF, Distler O, Flaherty KR, Frankel S, Oddis CV, Denton CP, Fischer A, Kowal-Bielecka OM, LeSage D, Merkel PA, Phillips K, Pittrow D, Swigris J, Antoniou K, Baughman RP, Castelino FV, Christmann RB, Christopher-Stine L, Collard HR, Cottin V, Danoff S, Highland KB, Hummers L, Shah AA, Kim DS, Lynch DA, Miller FW, Proudman SM, Richeldi L, Ryu JH, Sandorfi N, Sarver C, Wells AU, Strand V, Matteson EL, Brown KK, Seibold JRet al., 2013, Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials, Thorax, Vol: 69, Pages: 428-436, ISSN: 0040-6376

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF).Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed.Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Journal article

Singanayagam A, Manalan K, Sridhar S, Molyneaux PL, Connell DW, George PM, Kindelerer A, Seneviratne S, Lalvani A, Wickremasinghe M, Kon OMet al., 2013, Evaluation of screening methods for identification of patients with chronic rheumatological disease requiring tuberculosis chemoprophylaxis prior to commencement of TNF-α antagonist therapy, THORAX, Vol: 68, Pages: 955-961, ISSN: 0040-6376

Journal article

Thillai M, Potiphar L, Eberhardt C, Pareek M, Dhawan R, Kon OM, Wickremasinghe M, Wells A, Mitchell D, Lalvani Aet al., 2012, Obstructive lung function in sarcoidosis may be missed, especially in older white patients, EUROPEAN RESPIRATORY JOURNAL, Vol: 39, Pages: 775-777, ISSN: 0903-1936

Journal article

Mitchell DN, Wells A, Spiro SG, Moller DRet al., 2012, Sarcoidosis, Publisher: CRC Press, ISBN: 9780340992111

The book is fully comprehensive and evidence based and will be an essential addition to the bookshelves of all whose practice involves the care and treatment of patients with sarcoidosis.


Singanayagam A, Sridhar S, Dhariwal J, Abdel-Aziz D, Munro K, Connell DW, George PM, Molyneaux PL, Cooke GS, Burroughs AK, Lalvani A, Wickremasinghe M, Kon OMet al., 2012, A comparison between two strategies for monitoring hepatic function during antituberculous therapy, Am J Respir Crit Care Med, Vol: 185, Pages: 653-659, ISSN: 1535-4970

RATIONALE: The optimum strategy for monitoring liver function during antituberculous therapy is unclear. OBJECTIVES: To assess the value of the American Thoracic Society risk-factor approach for predicting drug-induced liver injury and to compare with a uniform policy of liver function testing in all patients at 2 weeks. METHODS: We conducted an observational study of adult patients undergoing therapy for active tuberculosis at a tertiary center. All patients had alanine transferase measurement at baseline and 2 weeks following commencement of therapy. Sensitivity, specificity, and positive and negative predictive values were used to assess strategies. MEASUREMENTS AND MAIN RESULTS: There were 288 patients included, and 21 (7.3%) developed drug-induced liver injury (57.1% "early" at 2 wk and 42.9% "late," after 2 wk). There were increased rates of individuals with HIV infection in the early drug-induced liver injury group compared with no drug-induced liver injury and late drug-induced liver injury groups (33% vs. 7.1% vs. 0%; P = 0.004). The American Thoracic Society algorithm had a sensitivity and specificity of 66.7 and 65.6%, respectively, for prediction of early and 22.2% and 63.7% for late drug-induced liver injury. The uniform monitoring policy had poor sensitivity but better specificity (22.2 and 82.1%) for prediction of late drug-induced liver injury. CONCLUSIONS: In our urban, ethnically diverse population, a risk-factor approach is neither sensitive nor specific for prediction of drug-induced liver injury. A uniform policy of liver function testing at 2 weeks is useful for prompt identification of a subgroup who develop early drug-induced liver injury and may offer better specificity in ruling out late drug-induced liver injury.

Journal article

Thillai M, Eberhardt C, Lewin AM, Potiphar L, Hingley-Wilson S, Sridhar S, Macintyre J, Kon OM, Wickremasinghe M, Wells A, Weeks ME, Mitchell D, Lalvani Aet al., 2012, Sarcoidosis and tuberculosis cytokine profiles: indistinguishable in bronchoalveolar lavage but different in blood, PLoS One, Vol: 7, ISSN: 1932-6203

BACKGROUND: The clinical, radiological and pathological similarities between sarcoidosis and tuberculosis can make disease differentiation challenging. A complicating factor is that some cases of sarcoidosis may be initiated by mycobacteria. We hypothesised that immunological profiling might provide insight into a possible relationship between the diseases or allow us to distinguish between them. METHODS: We analysed bronchoalveolar lavage (BAL) fluid in sarcoidosis (n = 18), tuberculosis (n = 12) and healthy volunteers (n = 16). We further investigated serum samples in the same groups; sarcoidosis (n = 40), tuberculosis (n = 15) and healthy volunteers (n = 40). A cross-sectional analysis of multiple cytokine profiles was performed and data used to discriminate between samples. RESULTS: We found that BAL profiles were indistinguishable between both diseases and significantly different from healthy volunteers. In sera, tuberculosis patients had significantly lower levels of the Th2 cytokine interleukin-4 (IL-4) than those with sarcoidosis (p = 0.004). Additional serum differences allowed us to create a linear regression model for disease differentiation (within-sample accuracy 91%, cross-validation accuracy 73%). CONCLUSIONS: These data warrant replication in independent cohorts to further develop and validate a serum cytokine signature that may be able to distinguish sarcoidosis from tuberculosis. Systemic Th2 cytokine differences between sarcoidosis and tuberculosis may also underly different disease outcomes to similar respiratory stimuli.

Journal article

George PM, Mehta M, Dhariwal J, Singanayagam A, Raphael CE, Salmasi M, Connell DW, Molyneaux P, Wickremasinghe M, Jepson A, Kon OMet al., 2011, Post-bronchoscopy sputum: Improving the diagnostic yield in smear negative pulmonary TB., Respir Med. 2011 Nov;105(11):1726-31

Journal article

Navani N, Molyneaux PL, Breen RA, Connell DW, Jepson A, Nankivell M, Brown JM, Morris-Jones S, Ng B, Wickremasinghe M, Lalvani A, Rintoul RC, Santis G, Kon OM, Janes SMet al., 2011, Utility of endobronchial ultrasound-guided transbronchial needle aspiration in patients with tuberculous intrathoracic lymphadenopathy: a multicentre study, THORAX, Vol: 66, Pages: 889-893, ISSN: 0040-6376

Journal article

Casey R, Blumenkrantz D, Millington K, Montamat-Sicotte D, Kon OM, Wickremasinghe M, Bremang S, Magtoto M, Sridhar S, Connell D, Lalvani Aet al., 2010, Enumeration of functional T-cell subsets by fluorescence-immunospot defines signatures of pathogen burden in tuberculosis, PLoS One, Vol: 5, ISSN: 1932-6203

BACKGROUND: IFN-gamma and IL-2 cytokine-profiles define three functional T-cell subsets which may correlate with pathogen load in chronic intracellular infections. We therefore investigated the feasibility of the immunospot platform to rapidly enumerate T-cell subsets by single-cell IFN-gamma/IL-2 cytokine-profiling and establish whether immunospot-based T-cell signatures distinguish different clinical stages of human tuberculosis infection. METHODS: We used fluorophore-labelled anti-IFN-gamma and anti-IL-2 antibodies with digital overlay of spatially-mapped colour-filtered images to enumerate dual and single cytokine-secreting M. tuberculosis antigen-specific T-cells in tuberculosis patients and in latent tuberculosis infection (LTBI). We validated results against established measures of cytokine-secreting T-cells. RESULTS: Fluorescence-immunospot correlated closely with single-cytokine enzyme-linked-immunospot for IFN-gamma-secreting T-cells and IL-2-secreting T-cells and flow-cytometry-based detection of dual IFN-gamma/IL-2-secreting T-cells. The untreated tuberculosis signature was dominated by IFN-gamma-only-secreting T-cells which shifted consistently in longitudinally-followed patients during treatment to a signature dominated by dual IFN-gamma/IL-2-secreting T-cells in treated patients. The LTBI signature differed from active tuberculosis, with higher proportions of IL-2-only and IFN-gamma/IL-2-secreting T-cells and lower proportions of IFN-gamma-only-secreting T-cells. CONCLUSIONS: Fluorescence-immunospot is a quantitative, accurate measure of functional T-cell subsets; identification of cytokine-signatures of pathogen burden, distinct clinical stages of M. tuberculosis infection and long-term immune containment suggests application for treatment monitoring and vaccine evaluation.

Journal article

Mehta MR, Connell DW, Wickremasinghe MI, Kon OMet al., 2010, The use of thoracic computed tomography scanning and EBUS-TBNA to diagnose tuberculosis of the central nervous system: two case reports., Eur Respir Rev, Vol: 19, Pages: 345-347

Herein, we report two cases of tuberculosis (TB) of the central nervous system where accessing the cerebrospinal fluid for diagnostic purposes was relatively or absolutely contraindicated at presentation. The finding of mediastinal lymphadenopathy on thoracic computed tomography scans, which was not visible on plain chest radiography, allowed endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of these lymph nodes to support the diagnosis of TB in each patient and rule out other disease processes. EBUS-TBNA is a new bronchoscopic technique and in this case report appears to be a safe and useful option in the diagnosis of TB. Moreover, it proved to be so in cases where the main focus of disease was outside the thorax.

Journal article

Bloch S, Wickremasinghe M, Wright A, Rice A, Thompson M, Kon OMet al., 2009, Paradoxical reactions in non-HIV tuberculosis presenting as endobronchial obstruction., Eur Respir Rev, Vol: 18, Pages: 295-299

Paradoxical reaction (PR) in tuberculosis (TB) is common and may affect up to 25% of patients. PR has the potential to cause significant morbidity and, on occasion, death. Although PR has been recognised for some time, the pathophysiology, especially in HIV-negative patients, is not well understood. We present two cases of PR in HIV-negative patients with TB presenting as significant airway obstruction secondary to a florid endobronchial component. These cases demonstrate that PR should be considered in all patients presenting with airway symptoms who have started TB treatment. The outcomes of the cases illustrate the need for wider recognition of this condition and more research to characterise patients who may be at risk, in order to gain a greater understanding of the mechanisms involved and to make or predict this diagnosis earlier.

Journal article

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