Anthony Edey

Lung Clearance Index and High-Resolution Computed Tomography Scores in Primary Ciliary Dyskinesia

RATIONALE Lung clearance index (LCI) is a more sensitive measure of lung function than spirometry in cystic fibrosis (CF) and correlates well with abnormalities in high-resolution computed tomography (HRCT) scanning. We hypothesized LCI would be equally sensitive to lung disease in primary ciliary dyskinesia (PCD). OBJECTIVES To test the relationships between LCI, spirometry, and HRCT in PCD and to compare them to the established relationships in CF. METHODS Cross-sectional study of 127 patients with CF and 33 patients with PCD, all of whom had spirometry and LCI, of which a subset of 21 of each had HRCT performed. HRCT was scored for individual features and these features compared with physiological parameters. MEASUREMENTS AND MAIN RESULTS Unlike in CF, and contrary to our hypothesis, there was no correlation between spirometry and LCI in PCD and no correlation between HRCT features and LCI or spirometry in PCD. CONCLUSIONS We show for the first time that HRCT, spirometry, and LCI have different relationships in different airway diseases and that LCI does not appear to be a sensitive test of airway disease in advanced PCD. We hypothesize that this results from dissimilarities between the components of large and small airway disease in CF and PCD. These differences may in part lead to the different prognosis in these two neutrophilic airway diseases.

Pulmonary function vascular index predicts prognosis in idiopathic interstitial pneumonia

Background and objective:  Pulmonary hypertension (PH) is associated with increased mortality in fibrotic idiopathic interstitial pneumonia (IIP). We hypothesize that baseline KCO (diffusing capacity of carbon monoxide/alveolar volume) and 6‐month decline in KCO reflect PH, thus predicting mortality in IIP.

Rituximab in autoimmune connective tissue disease–associated interstitial lung disease

OBJECTIVE CTD-associated interstitial lung disease (ILD) often fails to respond to conventional immunomodulatory agents. There is now considerable interest in the use of rituximab in systemic autoimmune CTD in patients refractory to standard treatments. The aim of this study was to review the experience of North Bristol NHS Trust managing patients with CTD-associated ILD with rituximab and explore possible associations with treatment response. METHODS We conducted a retrospective analysis of all patients who received rituximab under the Bristol CTD-ILD service, having failed to respond to other immunomodulatory treatments. Results were collated for pulmonary function and radiological outcomes before and after treatment. RESULTS Twenty-four patients were treated with rituximab. Their physiological parameters had failed to improve despite other immunomodulatory agents, with a mean change in forced vital capacity (FVC) prior to therapy of - 3.3% (95% CI - 5.6, -1.1) and mean change in diffusing capacity of carbon monoxide of - 4.3% (95% CI - 7.7, -0.9). After rituximab, radiology remained stable or improved for 11 patients, while worsening was observed in 9 patients. The decline in FVC was halted following treatment, with a mean change of + 4.1% (95% CI 0.9, 7.2), while diffusing capacity of carbon monoxide was stable [mean change +2.1% (95% CI - 1.0, 5.2)]. Patients with myositis overlap or antisynthetase syndrome appeared to respond well to treatment, with four patients showing clinically significant improvement in FVC >10%. CONCLUSION Rituximab is a therapeutic option in treatment-refractory CTD-associated ILD. Some disease subgroups may respond better than others, however, more work is needed to define its role in managing these patients.

Spontaneous pneumothorax: time to rethink management?

There are substantial differences in international guidelines for the management of pneumothorax and much geographical variation in clinical practice. These discrepancies have, in part, been driven by a paucity of high-quality evidence. Advances in diagnostic techniques have increasingly allowed the identification of lung abnormalities in patients previously labelled as having primary spontaneous pneumothorax, a group in whom recommended management differs from those with clinically apparent lung disease. Pathophysiological mechanisms underlying pneumothorax are now better understood and this may have implications for clinical management. Risk stratification of patients at baseline could help to identify subgroups at higher risk of recurrent pneumothorax who would benefit from early intervention to prevent recurrence. Further research into the roles of conservative management, Heimlich valves, digital air-leak monitoring, and pleurodesis at first presentation might lead to an increase in their use in the future.

Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection the alteplase dose assessment for pleural infection therapy project

Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open‐label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de‐escalation for intrapleural tPA. The first of several planned studies is presented here. Objectives: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Methods: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open‐label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C‐reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. Results: We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22‐58] to 16% [8‐31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247‐2,984] over 72 h of therapy; P < 0.05) and a reduction in blood C‐reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent surgery. Three patients (4.9%) received blood transfusions for gradual pleural blood loss; none were hemodynamically compromised. Pain requiring escalation of analgesia affected 36% of patients; none required cessation of therapy. Conclusions: These pilot data suggest that a starting dose of 5 mg of tPA administered intrapleurally twice daily in combination with 5 mg of DNase for the treatment of pleural infection is safe and effective. This regimen should be tested in future randomized controlled trials.

Pleural irrigation trial (PIT): a randomised controlled trial of pleural irrigation with normal saline versus standard care in patients with pleural infection

Pleural infection is increasing in incidence. Despite optimal medical management, up to 30% of patients will die or require surgery. Case reports suggest that irrigation of the pleural space with saline may be beneficial. A randomised controlled pilot study in which saline pleural irrigation (three times per day for 3 days) plus best-practice management was compared with best-practice management alone was performed in patients with pleural infection requiring chest-tube drainage. The primary outcome was percentage change in computed tomography pleural fluid volume from day 0 to day 3. Secondary outcomes included surgical referral rate, hospital stay and adverse events. 35 patients were randomised. Patients receiving saline irrigation had a significantly greater reduction in pleural collection volume on computed tomography compared to those receiving standard care (median (interquartile range) 32.3% (19.6–43.7%) reduction versus 15.3% (−5.5–28%) reduction) (p<0.04). Significantly fewer patients in the irrigation group were referred for surgery (OR 7.1, 95% CI 1.23–41.0; p=0.03). There was no difference in length of hospital stay, fall in C-reactive protein, white cell count or procalcitonin or adverse events between the treatment groups, and no serious complications were documented. Saline irrigation improves pleural fluid drainage and reduces referrals for surgery in pleural infection. A large multicentre randomised controlled trial is now warranted to evaluate its effects further. Does pleural irrigation improve pleural fluid drainage and resolution of sepsis in pleural infection? http://ow.ly/KPHeM

The Role of CT Pulmonary Angiography in the Investigation of Unilateral Pleural Effusions

Background: Pulmonary embolism (PE) is frequently cited as a common primary cause of unilateral pleural effusion, but in clinical practice appears to be uncommon. Objectives: In order to evaluate this observation, CT pulmonary angiography (CTPA) was performed in consecutive patients presenting to a single centre with a new uninvestigated unilateral pleural effusion and no clear cause and was supplemented by delayed-phase thoracic CT, optimized for visualization of the pleura. Methods: All patients underwent standard clinical assessment and pleural investigations in line with recent national guidelines and were followed up for a minimum of 1 year or until histological/microbiological diagnosis. Results: One hundred and fifty patients were recruited, and of these, 141 had a CTPA. PEs were detected in 9/141 (6.4%) patients, and of these, 8/9 were subsequently diagnosed with pleural malignancy. In only 1 case was PE clinically suspected and in no case was PE the primary cause of effusion; 9.8% (8/82) of patients who were ultimately diagnosed with pleural malignancy had PE at presentation. Conclusions: This study indicates that PE is a frequent concomitant finding in patients with malignant effusions but uncommon as a primary cause of unilateral effusion. In addition, it highlights the known difficulty of clinical diagnosis of PE in the context of malignancy. In view of this, we recommend that CTPA combined with pleural-phase thoracic CT should be considered at presentation when investigating patients with suspected malignant pleural effusion.

Thoracic complications of rheumatoid disease

Rheumatoid arthritis is a relatively common multisystem disease associated with significant mortality and morbidity. Thoracic disease, both pleural and pulmonary, is a frequent extra-articular manifestation of rheumatoid arthritis and responsible for approximately 20% of rheumatoid-associated mortality. Rheumatoid disease and its associated therapies can affect all compartments of the lung inciting a range of stereotyped pathological responses and it is not infrequent for multiple disease entities to co-exist. In some instances, development of pulmonary complications may precede typical rheumatological presentation of the disease and be the first indication of an underlying connective tissue disease. The spectrum of thoracic disease related to rheumatoid arthritis is reviewed.

Differentiating benign from malignant mediastinal lymph nodes visible at EBUS using grey-scale textural analysis.

Recent data suggest that grey‐scale textural analysis on endobronchial ultrasound (EBUS) imaging can differentiate benign from malignant lymphadenopathy. The objective of studies was to evaluate grey‐scale textural analysis and examine its clinical utility.

S17 Pleural Irrigation Trial (PIT): Standard Care Versus Pleural Irrigation, a Randomised Controlled Trial in Patients with Pleural Infection

Background Pleural infection remains common with an increasing incidence. It is associated with a high morbidity and mortality. Despite chest tube drainage and antibiotic therapy up to 30% of patients will die or require surgery. Case reports suggest that irrigation of the pleural space with saline may be beneficial but this has never been the tested in the form of a randomised controlled trial. Method Randomised controlled pilot study comparing saline irrigation (250ml normal saline intra-pleurally over one hour, 3 times a day for 3 days) plus best standard care, with best standard care alone, in patients with pleural infection (microbiology positive or pH<7.2 or purulent pleural fluid and clinical infection) requiring chest tube drainage, who had a residual pleural collection on baseline CT thorax. Primary outcome was percentage change in CT pleural volume from day 0 to day 3. Secondary outcomes included referral for surgery, hospital stay and adverse events. Results 47 patients approached, 38 randomised, 3 excluded (drain fell out/no residual fluid on CT/removal of consent). Saline irrigation results in significant reduction in CT pleural collection volume compared to standard care – Irrigation group 29.15% reduction (95% CI 16.2–62) vs Standard care 13.9% (95% CI –4.1–26.3) p<0.04. There was also a significant reduction in the need for thoracic surgery in the irrigation group 9/17 vs 2/18 p=0.01 (OR 9.0, 95% CI 1.56–51.9). No differences were seen in length of hospital stay or fall in inflammatory markers (CPR, WCC and procalcitinin). The safety profile of saline irrigation was good with no serious complications and adverse events did not differ between groups. Conclusion Saline irrigation improves fluid drainage in pleural infection (as measured by volumetric CT), leading to reduction in referral for surgery. No change in hospital stay was noted. This study now needs to be repeated as a large multicentre RCT powered to look at mortality and length of hospital stay.