Papers by Dermot O'Callaghan
Respiratory Medicine Extra, 2006
A 58-year-old male smoker presented with pyrexia, dyspnoea and cough productive of green sputum. ... more A 58-year-old male smoker presented with pyrexia, dyspnoea and cough productive of green sputum. Chest X-ray revealed a left upper lobe infiltrate and three nodules in the left mid and lower zones. This X-ray also revealed evidence of previous atlanto-axial ...
Thoracic and Cardiovascular Surgeon, Nov 14, 2008
Primary cardiac angiosarcoma is a rare tumor that may present with features mimicking venous thro... more Primary cardiac angiosarcoma is a rare tumor that may present with features mimicking venous thromboembolic disease, making the diagnosis particularly challenging. Without a high index of suspicion, the majority of cases will remain undetected until the disease is advanced. As a result, the outlook for most patients remains dismal even with aggressive multimodality treatment. We report a case of angiosarcoma masquerading as recurrent pulmonary embolism successfully treated by radical surgery and adjuvant cytotoxic chemotherapy.
Chest, Oct 1, 2014
PURPOSE: Haemoptysis ia a common symptom in patients presenting to a rapid access lung cancer cli... more PURPOSE: Haemoptysis ia a common symptom in patients presenting to a rapid access lung cancer clinic (RALC) and its evaluation currently utilises significant resources. METHODS: Medical records of all patients referred to two national tertiary RALC referral centers (assessment time <2wks) with haemoptysis who underwent computed tomography (CT) scanning and bronchoscopy over a one year period were reviewed. The gold standard for the cause of haemoptysis was a composite of endoscopic, radiological, pathological and microbiological diagnosis, with at least 6 months clinico-radiological follow up. CT findings were sub-categorised into those with or without an attributable cause for haemotpysis. RESULTS: Out of 1159 RALC referrals, 257 (22%) patients (143M, 114 F) reported haemoptysis and all underwent CT scanning and bronchoscopy. 167 (65%) patients had an attributable cause for haemoptysis identified on CT (lung cancer n=64; infection n=83; bronchiectasis n=16; and pulmonary embolism n=2). A histological diagnosis of lung cancer from bronchoscopic sampling was established in 44/64 cases. In subgroup analysis, patients with haemoptysis >14 days duration had an increased liklihood of lung cancer in comparison to infection (p<0.05). There were no false negative CT scans for lung cancer. CONCLUSIONS: One quarter of patients referred to our RALC with haemoptysis had lung cancer. No patient presenting with haemotysis had a false negative CT for lung cancer. In subgroup analysis, patients with persistent haemoptysis were more likely to have lung cancer. CLINICAL IMPLICATIONS: State of the art CT imaging of the thorax is highly sensitive at excluding lung cancers large enough to cause haemoptysis.
The American Journal of Medicine, Mar 1, 2010
Funding: SP Gaine has received speaking honoraria and attended advisory board meetings of many of... more Funding: SP Gaine has received speaking honoraria and attended advisory board meetings of many of the pharmaceutical companies involved in pulmonary arterial hypertension in the past year, including Actelion, Pfizer, Lung Rx, and GSK. He has no investment or stock interest in any pharmaceutical company. DM Murphy and DS O'Callaghan previously have received funding as recipients of European Respiratory Society Fellowships.
Clinics in Chest Medicine, Dec 1, 2013
Macitentan (Opsumit) is a new dual endothelin receptor antagonist with reduced risk of hepatotoxi... more Macitentan (Opsumit) is a new dual endothelin receptor antagonist with reduced risk of hepatotoxicity and drug interactions, that only requires once-daily dosing. The phase III SERAPHIN trial showed this drug reduced a combined morbidity and mortality end point in pulmonary arterial hypertension by 50% compared with controls. Previously developed oral prostacyclin analogues have limited efficacy. However, prostacyclin I receptor agonists, of which selexipag (ACT-293987) is the first in class, may be more effective. A phase II study of this orally active agent showed a 30% reduction in pulmonary vascular resistance, and a phase III study is underway. Riociguat (BAY63-2521) is a guanylate cyclase stimulator that has demonstrated positive effects on exercise capacity in phase III studies evaluating patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Other new potential treatments that require further investigation include rho-kinase inhibitors, dichloroacetate, angiotensin-converting enzyme 2 inhibitors, receptors for advanced glycation end products (RAGE) inhibitors, chemical chaperones for mutations associated with pulmonary arterial hypertension, and endothelial progenitor cells.
Respiratory Medicine, Jul 1, 2010
Presse Medicale, 2016
Le traitement des formes sévères d'hypertension artérielle pulmonaire repose sur l'administration... more Le traitement des formes sévères d'hypertension artérielle pulmonaire repose sur l'administration de prostacyclines intraveineuse à l'aide d'un cathéter veineux central tunnélisé. Les infections liées au cathéter sont des complications fréquentes inhérentes au dispositif. Trois tableaux cliniques peuvent être observés : les infections locales, les tunnelites et les bactériémies. Le tableau clinique peut être bruyant ou fruste, compliquant son diagnostic. Il faut savoir évoquer une infection de cathéter devant toute aggravation inexpliquée de l'HTAP même en l'absence de signes locaux ou généraux d'infection. Les infections liées au cathéter sont grevées d'une morbimortalité significative allant d'une aggravation de l'HTAP au décès. Leur détection et leur prise en charge précoce sont primordiales. En cas de traitement par époprosténol intraveineux, les germes les plus fréquemment identifiés sont les staphylocoques coagulase négatif, les microcoques et les staphylocoques dorés. Chez les patients traités par tréprostinil, les infections à bactéries à gram négatif sont les plus fréquentes. Les infections locales nécessitent un traitement local alors qu'en cas de tunnelites ou de bactériémies, l'administration d'une antibiothérapie systémique et le retrait du cathéter sont indispensables. La prévention des infections liées aux cathéters repose sur l'éducation des patients, de leurs aidants et des soignants et l'application de mesures strictes d'asepsie. Disponible sur internet le : Pour citer cet article : Boucly A, et al. Infections liées aux cathéters veineux centraux tunnélisés chez les patients ayant une hypertension artérielle pulmonaire traitée par prostacycline intraveineuse. Presse Med. (2015),
International Journal of Clinical Practice, Dec 22, 2010
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Expert Opinion on Pharmacotherapy, Apr 20, 2011
Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin, internal... more Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin, internal organs, and widespread vasculopathy. Raynaud's phenomenon and digital ulcers are vascular manifestations of this disease and cause significant morbidity. Current treatments are only moderately effective in reducing the severity of Raynaud's in a portion of patients and typically do not lead to substantial benefit in terms of the healing or prevention of digital ulcers. Several studies have evaluated the efficacy of targeting the vasoconstrictor endothelin-1 for the treatment of systemic sclerosis-associated vascular disease. The purpose of this paper is to summarize the published studies and case reports evaluating the efficacy of endothelin receptor antagonists in the treatment of Raynaud's phenomenon and digital ulcers associated with systemic sclerosis.
The European respiratory journal, Jul 7, 2011
The mean pulmonary artery pressure (Ppa) achieved on mild-to-moderate exercise is age related and... more The mean pulmonary artery pressure (Ppa) achieved on mild-to-moderate exercise is age related and its haemodynamic correlates remain to be documented in patients free of pulmonary hypertension (PH). Our retrospective study involved patients free of PH investigated in our centre for possible pulmonary vascular disease between January 1, 2007 and October 31, 2009 who underwent right heart catheterisation at rest and during supine exercise up to 60 W. The 38 out of 99 patients aged ,50 yrs were included and a Ppa of 30 mmHg was considered the upper limit of normal on exercise. The 24 subjects who developed Ppa.30 mmHg on exercise had higher resting Ppa (19¡3 versus 15¡4 mmHg) and indexed pulmonary vascular resistance (PVRi; 3.4¡1.5 versus 2.2¡1.1 WU?m 2 ; p,0.05) than the remaining 14 subjects. Resting Ppa .15 mmHg predicted exercise Ppa .30 mmHg with 88% sensitivity and 57% specificity. The eight patients with resting Ppa 22-24 mmHg all had exercise Ppa .30 mmHg. In subjects aged ,50 yrs investigated for possible pulmonary vascular disease and free of PH, patients with mild-to-moderate exercise Ppa .30 mmHg had higher resting PVRi and higher resting Ppa, although there was no resting Ppa threshold value that could predict normal response on mild-to-moderate exercise. The clinical relevance of such findings deserves further long-term follow-up studies.
European Respiratory Review, Aug 31, 2012
Pulmonary arterial hypertension (PAH) is a rare disease characterised by a progressive increase i... more Pulmonary arterial hypertension (PAH) is a rare disease characterised by a progressive increase in pulmonary vascular resistance, leading to right heart failure and premature death. Over the last two decades, a better understanding of the pathogenesis of PAH has led to the approval of several targeted therapies that confer improvements in patients' clinical and haemodynamic status, quality of life and survival. Analysis of recent survival data in PAH cohorts have been biased by the inclusion of prevalent patients included months or years after PAH diagnosis (''survivors'') who have a better prognosis than corresponding incident patients diagnosed at the time of recruitment. A critical analysis of recent multicentre incident cohorts has shown survival improvements in the current management era. However, idiopathic PAH remains a severe disease and still carries a poor prognosis. Modern survival figures also highlight the relevance of lung transplantation in eligible PAH patients who are refractory to current best standard of medical care.
Expert Review of Respiratory Medicine, Apr 1, 2011
Pulmonary veno-occlusive disease (PVOD) is a rare disorder that can be misdiagnosed as idiopathic... more Pulmonary veno-occlusive disease (PVOD) is a rare disorder that can be misdiagnosed as idiopathic pulmonary arterial hypertension (PAH) and accounts for 5-10% of cases initially considered as idiopathic PAH. PVOD and idiopathic PAH share a similar clinical presentation, genetic background and hemodynamic profile. A definite diagnosis of PVOD necessitates a surgical biopsy, but since it represents a high-risk procedure in these patients, it is contraindicated. Therefore, a noninvasive diagnostic approach using chest high-resolution computed tomography, arterial blood gas analysis, pulmonary function tests and bronchoalveolar lavage is helpful to detect PVOD. PVOD is characterized by a poor prognosis and the possibility of developing severe pulmonary edema with specific PAH therapy. Lung transplantation remains the treatment of choice.
Clinics in Chest Medicine, Mar 1, 2007
This review assesses the available evidence supporting the use of drug combinations for the manag... more This review assesses the available evidence supporting the use of drug combinations for the management of the various forms of pulmonary arterial hypertension (PAH). Ongoing and forthcoming randomized trials evaluating this strategy are also highlighted. Furthermore, new types of agents to treat PAH in the future are explored.
The European respiratory journal, Nov 5, 2015
The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We ... more The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis. Tumour-and stroma-infiltrating CD3 + , CD8 + and forkhead box P3 (Foxp3) + T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined. There was a positive association between overall survival and increased CD8 + TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3 + TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8 + islet (HR 0.48, p<0.001) and Foxp3 + stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3 + and CD8 + stromal counts and high Foxp3 + islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8 + TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3 + TI/S ratio was associated with worse survival (HR 3.91, p<0.001). Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.
Journal of Heart and Lung Transplantation, Feb 1, 2012
BACKGROUND: Recent guidelines have proposed first-line combination therapy as a potential strateg... more BACKGROUND: Recent guidelines have proposed first-line combination therapy as a potential strategy for the treatment of functional class IV pulmonary arterial hypertension (PAH). METHODS: We analyzed efficacy and safety of upfront epoprostenol and bosentan combination therapy in consecutive patients with idiopathic, heritable, or anorexigen-associated PAH and compared outcomes with matched controls treated by epoprostenol monotherapy. RESULTS: Data for 16 functional class III patients and 7 functional class IV patients were analyzed. Baseline 6-minute walk distance (6MWD) was 287 Ϯ 133 meters, mean pulmonary artery pressure was 65 Ϯ 12 mm Hg, cardiac index was 1.8 Ϯ 0.3 L/min/m 2 , and pulmonary vascular resistance (PVR) was 1493 Ϯ 398 dynes/sec/cm 5. After 4 months, 6MWD and PVR significantly improved to 421 Ϯ 100 meters and 784 Ϯ 364 dynes/sec/cm 5 , respectively. These improvements were maintained long-term (30 Ϯ 19 months). At 1, 2, 3, and 4 years, overall survival estimates were 100%, 94%, 94%, and 74%, and transplant-free survival estimates were 96%, 85%, 77%, and 60%, respectively. Compared with matched controls started on epoprostenol monotherapy, there was a trend to an improvement in overall survival (p ϭ 0.07). CONCLUSIONS: Initial combination therapy with epoprostenol and bosentan in patients with severe PAH is associated with improvements in important outcomes such as functional class, exercise capacity, and hemodynamics. This combination strategy might also favorably affect overall and transplant-free survival.
The European respiratory journal, May 31, 2012
Data on treatment of patients with portopulmonary hypertension (PoPH) are limited, as they are us... more Data on treatment of patients with portopulmonary hypertension (PoPH) are limited, as they are usually excluded from randomised controlled trials with pulmonary arterial hypertension (PAH)-specific therapies. This study investigated the short-and long-term efficacy/safety of bosentan in these patients, as well as its pharmacokinetics. All 34 consecutive patients with PoPH treated with first-line bosentan (December 2002 to July 2009) were retrospectively evaluated. Assessments included the New York Heart Association functional class (NYHA FC), blood tests, haemodynamics, 6-min walk distance (6MWD) and eventfree status. The pharmacokinetics of bosentan in five patients with Child-Pugh (C-P) class B cirrhosis were compared with idiopathic PAH patients. Significant improvements from baseline were observed in NYHA FC, 6MWD and haemodynamics, and were largely maintained during follow-up. Patients with C-P class B cirrhosis (n59) had significantly larger haemodynamic improvement after mean¡SD 5¡2 months. Mean followup time was 43¡19 months; four patients died and seven patients had significant elevation of liver enzymes (annual rate 5.5%). Plasma concentrations of bosentan were higher in patients with C-P class B cirrhosis than those observed in idiopathic PAH. These data confirm the benefit of bosentan treatment for patients with PoPH. Haemodynamic improvements were particularly pronounced in patients with more severe cirrhosis. The safety profile of bosentan was consistent with previous studies.
Journal of Thoracic Oncology, Dec 1, 2010
The link between chronic immune activation and tumorigenesis is well established. Compelling evid... more The link between chronic immune activation and tumorigenesis is well established. Compelling evidence has accumulated that histologic assessment of infiltration patterns of different host immune response components in non-small cell lung cancer specimens helps identify different prognostic patient subgroups. This review provides an overview of recent insights gained in the understanding of the role played by chronic inflammation in lung carcinogenesis. The usefulness of quantification of different populations of lymphocytes, natural killer cells, macrophages, and mast cells within the tumor microenvironment in non-small cell lung cancer is also discussed. In particular, the importance of assessment of inflammatory cell microlocalization within both the tumor islet and surrounding stromal components is emphasized.
Ejc Supplements, Oct 1, 2009
European Respiratory Review, May 31, 2013
We present the case of a patient with pulmonary cavitation of extremely unusual aetiology, which ... more We present the case of a patient with pulmonary cavitation of extremely unusual aetiology, which presented a significant diagnostic challenge despite multidisciplinary involvement. A 54-year-old male presented with a 6-week history of haemoptysis associated with fatigue, night sweats and dyspnoea. His past medical history was significant for coronary artery stenting (treated with aspirin). There was no history of exposure to tuberculosis. He had a 50-pack-year smoking history, prior excessive alcohol consumption and had worked in construction, though denied asbestos exposure. On physical examination, vital signs were normal, his dentition was poor, there was no digital clubbing and chest auscultation was unremarkable.
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Papers by Dermot O'Callaghan