Michael T. Henry

Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids.

We would like to report our experience of using rituximab in cyclophosphamide refractory, rapidly progressive interstitial lung disease (ILD) in a patient with limited scleroderma. A 40-year-old man presented with 10-week history of inflammatory polyarthritis, which responded to a short course of oral corticosteroids. However, 3 weeks later, he developed new onset of exertional dyspnoea. High-resolution CT of the thorax was suggestive of early ILD. Surgical lung biopsy showed features of fibrotic non-specific interstitial pneumonia. He was diagnosed with scleroderma on the basis of: presence of anticentromere antibodies, Raynaud’s phenomenon, pulmonary fibrosis, digital oedema and hypomotility along with a dilated oesophagus. He was treated aggressively with pulse doses of corticosteroids and cyclophosphamide; however, his ILD continued to deteriorate. At this stage, he received rituximab (two pulses of 1 g each), which led to a gradual clinical improvement. Now, 12 months since his rituximab infusion, he walks 2 miles daily without any exertional dyspnoea.

Idiopathic pulmonary fibrosis: Treatment update

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Despite multiple recent clinical trials, there is no strong evidence supporting a survival advantage for any agent in the management of patients with IPF. The limited effectiveness of current treatment regimes has led to a search for novel therapies including antifibrotic strategies. This article reviews the evidence supporting the treatments currently used in the management of IPF.

A study to assess inhaler technique and its potential impact on asthma control in patients attending an asthma clinic

Abstract Objectives: The aim of this study was to evaluate inhaler technique and symptom control in patients with poorly controlled asthma at baseline and at follow-up in a dedicated asthma clinic in a tertiary hospital. We also investigated the impact of asthma on these patients’ quality of life. Methods: Patients referred to a newly established asthma clinic in Cork University Hospital were prospectively recruited over a 6-month period. Their inhaler technique was assessed by a pulmonary nurse specialist using a validated scoring system. They received instruction on inhaler usage when scores were suboptimal. Patients completed a validated asthma control questionnaire (ACQ) and asthma quality of life questionnaire (AQLQ). At follow-up 3–4 months later, the inhaler technique was reassessed and the ACQ questionnaire repeated. Results: Forty-six patients were recruited (female = 74%), and 40/46 were followed up. Mean [SD] FEV1 % predicted at baseline = 76.5% [21.5]. About 63% of the patients were classified as incorrectly using their inhaler at their initial assessment. This decreased to 20% at follow-up, indicating an overall significant improvement in inhaler usage post-training (p = 0.003). ACQ scores improved significantly from median [interquartile range] 2.70 [1.66] to 2.00 [1.90] (p = 0.002). Baseline measurement indicated that patients’ quality of life was moderately affected by asthma, with a median AQLQ score of 4.75 [1.97]. Conclusion: This study demonstrates the importance of educating and formally assessing inhaler technique in patients with asthma as a part of their ongoing clinical review.

Progestogens and Cushing's syndrome.

We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused clinical hypercortisolism and Cushing’s syndrome. Studies of the toxicity of Medroxyprogesterone Acetate list the commonest adverse events at 500 mg/day as weight gain, water retention, increased blood pressure, tremor, moon face, sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid-like effects are seen in up to 30% of patients treated for longer than 6 weeks with mostly large doses of the order of 1500 mg/day but Cushing’s syndrome has been reported in patients taking 400 mg/day. Neither the glucocorticoid-like effects or Cushing’s syndrome have been previously observed with Megestrol Acetate. In the elderly female population receiving progestogens for neoplastic disease the progestogen itself could be an appreciable cause of morbidity both by causing glucocorticoid-like effects and Cushing’s syndrome but also by lack of awareness of the danger of sudden withdrawal of these compounds when the hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms could be easily overlooked unless appropriate testing for Cushing’s syndrome is carried out. While the progestogen may have to be continued indefinitely a dose decrease may be feasible with reduction of morbidity.

Increasing the accuracy of 18F-FDG PET/CT interpretation of “mildly positive” mediastinal nodes in the staging of non-small cell lung cancer

INTRODUCTION The aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC). METHODS This was a retrospective, interdisciplinary, per-node analysis study. We included patients with NSCLC and mediastinal nodes with an SUV max in the range of 2.5-4.0 on PET-CT. We hypothesized that the greatest number of false positive cases would occur in this cohort of patients. RESULTS A total of 92 mediastinal lymph nodes were analyzed in 44 patients. Mediastinal disease (N2/N3) was histologically confirmed in 15 of 44 patients and in 34 of 92 lymph nodes; positive predictive value of 37% and false positive rate of 63%. Lymph node SUV max, tumor size, ratio of node SUV max to tumor SUV max (SUVn/SUVp), and ratio of node SUV max to node size (SUV n/SADn) were significantly higher in true positive cases. Using a threshold of 0.3 for SUV node/tumor and 3 for SUV node/size yielded sensitivities of 91% and 71% and specificities of 71% and 69% respectively for the detection of mediastinal disease. Using both ratios in combination resulted in a sensitivity of 65% and a specificity of 88%. Concurrent benign lung disease was observed significantly more frequently in false-positive cases. CONCLUSION SUVn/SUVpt and SUVn/SADn may be complimentary to conventional visual interpretation and SUV max measurement in the assessment of mediastinal disease in patients with NSCLC.

Communication of unexpected and significant findings on chest radiographs with an automated PACS alert system.

PURPOSE An integral part of realizing the enormous potential of imaging in patient care is close communication between radiologists and referring physicians. One key element of this process is the communication of unexpected significant findings. The authors examined the performance of a PACS-based alert system in the appropriate communication of reports containing unexpected significant findings to referring physicians. METHODS A PACS-integrated key word system was developed such that an e-mail was sent to the referring clinician if a radiologist detected a significant unexpected finding. The number, source, and outcome of chest radiographic unexpected findings over a 14-month period were analyzed. The time for response of the referring physician plus time for follow-up were also examined. RESULTS Key words were applied to 158 of the 39,665 chest radiographs (0.4%) obtained during the study period. The emergency department was the most frequent referral location (46.2%). Final diagnostic categories included malignancy (13.9%), benign lesion (49.4%), and no abnormality (20.2%). The average time to acknowledgment by clinicians of notification was 3.1 days, although 57.6% were acknowledged within 24 hours. The mean time interval to the next relevant radiologic investigation was 26 days among the 77.8% of findings that underwent radiologic follow-up. CONCLUSIONS The development of electronic alert systems, which are integrated into PACS, can aid greatly in report communication and eliminate the risk associated with unread reports that contain significant or unexpected findings.

CT Densitometry as a Predictor of Pulmonary Function in Lung Cancer Patients

Purpose: Preoperative pulmonary assessment is undertaken in patients with resectable lung cancer to identify those at increased risk of perioperative complications. Guidelines from the American College of Chest Physicians indicate that if the FEV1 and DLCO are ≥60% of predicted, patients are suitable for resection without further evaluation. The aim of our study is to determine if quantitative measures of lung volume and density obtained from pre-operative CT scans correlate with pulmonary function tests. This may allow us to predict pulmonary function in patients with lung cancer and identify patients who would tolerate surgical resection. Materials and Methods: Patients were identified retrospectively from the lung cancer database of a tertiary hospital. Image segmentation software was utilized to estimate total lung volume, normal lung volume (values -500 HU to -910 HU), emphysematous volume (values less than -910 HU), and mean lung density from pre-operative CT studies for each patient and these values were compared to contemporaneous pulmonary function tests. Results: A total of 77 patients were enrolled. FEV1 was found to correlate significantly with the mean lung density (r=.762, p<.001) and the volume of emphysema (r= -.678, p<.001). DLCO correlated significantly with the mean lung density (r =.648, p<.001) and the volume of emphysematous lung (r= -.535, p<.001). Conclusion: The results of this study suggest that both FEV1 and DLCO correlate significantly with volume of emphysema and mean lung density. We now plan to prospectively compare these CT parameters with measures of good and poor outcome postoperatively to identify CT measures that may predict surgical outcome preoperatively

Spontaneous pneumomediastinum in a patient with anti-centromere antibody-positive limited scleroderma.

T he patient, a 40-year-old man, presented to our rheumatology outpatient department with increasing pain and swelling of the small joints of hands and wrists, and painful and stiff knees and ankles. He also experienced profound early morning stiffness, which lasted for 2 hours. Apart from Raynaud phenomenon and gastroesophageal reflux disease, there were no features to suggest connective tissue disease. Examination revealed synovitis affecting his wrists and multiple metacarpal phalangeal joints. On laboratory tests, he had negative anti/cyclic citrullinated peptide antibodies, positivity for antinuclear antibodies and anti/centromere antibodies, and mildly raised inflammatory markersVC-reactive protein of 42 mg/L (reference range, 1Y10 mg/L) and ESR of 29 mm/hr (reference range G30 mm/hr). He was commenced on oral corticosteroids. However, within a month, he presented with a new development of exertional dyspnea. Further investigations in May 2009 (high-resolution computed tomography [CT] scan of the thorax, pulmonary function tests, mediastinoscopy, and video-assisted thoracic surgery lung biopsy) revealed that he had an underlying interstitial cellular and fibrotic process highly suggestive of nonspecific interstitial pneumonia; this was considered pulmonary involvement (interstitial lung disease) because of scleroderma. He was then diagnosed with scleroderma on the following basis: the presence of disease-specific autoantibodies (anti/centromere antibodies), Raynaud phenomenon, pulmonary fibrosis, and dilated esophagus. Oral corticosteroids (1 mg/kg) and intravenous monthly cyclophosphamide for scleroderma-associated interstitial lung disease were administered. In September 2009, he presented with sudden worsening of his exertional dyspnea. Chest x-ray showed no acute deterioration. High-resolution CT of the thorax was requested, and to our surprise, this showed free air in the anterior and middle mediastinum. He was diagnosed to have spontaneous pneumomediastinum, and this resolved completely on conservative management with bed rest, supplemental oxygen, analgesia, and close observation (Fig.). Spontaneous pneumomediastinum is typically a benign and self-limited disorder. Dyspnea, as in our case, is one of the common symptoms; this may be due to associated chest discomfort, which typically is worsened by inspiratory maneuvers. Spontaneous pneumomediastinum can mimic the worsening of associated disease, such as interstitial lung disease. Chest radiographs and CT scans are important in confirming the diagnosis of spontaneous pneumomediastinum. In such cases, the mainstay of management remains conservative, and once resolved, no restriction in physical activity is required. Although, few cases of spontaneous pneumomediastinum as a complication of systemic scleroderma (antiYscl-70 positive) have been reported, this is the first reported case of spontaneous pneumomediastinum in a patient with limited scleroderma with anti/centromere antibodies. In addition to the development or worsening of interstitial lung disease and/or pulmonary hypertension, new-onset dyspnea in a patient with scleroderma should prompt evaluation for other causes. For example, in our patient, acute worsening of dyspnea was attributed to development of spontaneous pneumomediastinum. Moreover, as our patient had rapidly progressive pulmonary fibrosis, this pneumomediastinum is likely secondary to the rupture of subpleural cysts. The patient developed pneumomediastinum 4 months after undergoing lung biopsy, so it is highly unlikely that the procedure would have caused the pneumomediastinum. Similarly, there was no evidence of esophageal rupture causing this pneumomediastinum. This case highlights the importance of considering spontaneous pneumomediastinum in the differential diagnoses of sudden worsening of dyspnea in a patient with scleroderma. Spontaneous pneumomediastinum should be considered as a possible alternative in a patient with sudden worsening of dyspnea in a patient with scleroderma. From the Departments of *Rheumatology, †Radiology, and ‡Respiratory Medicine, Cork University Hospital, Cork, Ireland. Correspondence: Muhammad Haroon, MB, MMedSc, MRCPI, Department of Rheumatology, Cork University Hospital, Cork, Ireland. E-mail: mharoon301@hotmail.com. Copyright * 2010 by Lippincott Williams & Wilkins ISSN: 1076-1608/11/1701Y0042 DOI: 10.1097/RHU.0b013e3182055d5e FIGURE. Axial high-resolution chest CT images from September 2009 (series A), October 2009 (series B), and May 2010 (series C). Images from series A demonstrate gas in the anterior and middle mediastinum. Subsequent images (series B and C) show a successive decrease in volume of pneumomediastinum with no residual gas in series C. CONCISE REPORT

Bronchoscopy in the investigation of outpatients with hemoptysis at a lung cancer clinic

BACKGROUND In the investigation of lung cancer, current practice in many healthcare systems would support bronchoscopy regardless of CT findings in patients with hemoptysis. We sought to identify the cause, the diagnostic yield of CT and bronchoscopy and the requirement for bronchoscopy in at risk patients with hemoptysis with a normal CT scan through our rapid access lung cancer clinic (RALC). METHODS Initially, a chart review was performed on all patients with hemoptysis (2011-2012) and thereafter a prospective analysis was performed (2013-2016). RESULTS Our analysis represents the largest study to date in outpatients with hemoptysis. In our retrospective study, 155 patients reported hemoptysis. Causes were lower respiratory tract infections (RTIs) (47%) and lung cancer (16%). Our prospective study included 182 patients. The causes of hemoptysis were RTIs (50%) and lung cancer (18%). There were no false negative CT-scans for lung cancer. 47/57 present with lung cancer underwent bronchoscopy and 43/47 were positive for lung cancer (92%). Patients with hemoptysis and lung cancer have a higher stage of malignancy with a predominance of squamous cell lung carcinoma. Smoking status, the duration of hemoptysis or description of hemoptysis were not predictive of lung cancer however lung cancer was not identified in patients age <50. CONCLUSIONS One sixth of patients presenting with hemoptysis to our lung cancer clinic had lung cancer. No patient identified with cancer related haemoptysis had a CT negative for lung cancer and a combination of bronchoscopy plus endobronchial ultrasound trans-bronchial needle aspiration (EBUS-TBNA) in those patients with a CT suspicious of lung cancer is 92% sensitive for lung cancer causing hemoptysis.

Investigating idiopathic inflammatory myopathy; initial cross speciality experience with use of the extended myositis antibody panel

The discovery of unique autoantibodies has informed and altered our approach to the diagnosis and management of the inflammatory myopathies. This study reports the initial clinical experience of use of the Extended Myositis Antibody (EMA) panel in the largest university teaching hospital in Ireland. We conducted a retrospective review of all patients who had serum samples tested for myositis specific antibodies and myositis associated antibodies from April 2014 to March 2015. A positive EMA panel was of significant clinical utility in facilitating decisions on appropriate investigations, and need for onward referral to other physicians. Furthermore, this paper highlights the diversity of possible presentations of idiopathic inflammatory myopathy with subsequent need for multi-speciality involvement, and serves to heighten awareness among clinicians of the diagnostic use of extended myositis antibody testing in these cases.