Christopher W. H. Davies

Effect of an Indwelling Pleural Catheter vs Chest Tube and Talc Pleurodesis for Relieving Dyspnea in Patients With Malignant Pleural Effusion: The TIME2 Randomized Controlled Trial

CONTEXT Malignant pleural effusion causes disabling dyspnea in patients with a short life expectancy. Palliation is achieved by fluid drainage, but the most effective first-line method has not been determined. OBJECTIVE To determine whether indwelling pleural catheters (IPCs) are more effective than chest tube and talc slurry pleurodesis (talc) at relieving dyspnea. DESIGN Unblinded randomized controlled trial (Second Therapeutic Intervention in Malignant Effusion Trial [TIME2]) comparing IPC and talc (1:1) for which 106 patients with malignant pleural effusion who had not previously undergone pleurodesis were recruited from 143 patients who were treated at 7 UK hospitals. Patients were screened from April 2007-February 2011 and were followed up for a year. INTERVENTION Indwelling pleural catheters were inserted on an outpatient basis, followed by initial large volume drainage, education, and subsequent home drainage. The talc group were admitted for chest tube insertion and talc for slurry pleurodesis. MAIN OUTCOME MEASURE Patients completed daily 100-mm line visual analog scale (VAS) of dyspnea over 42 days after undergoing the intervention (0 mm represents no dyspnea and 100 mm represents maximum dyspnea; 10 mm represents minimum clinically significant difference). Mean difference was analyzed using a mixed-effects linear regression model adjusted for minimization variables. RESULTS Dyspnea improved in both groups, with no significant difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC group (95% CI, 19.3-30.1 mm) and 24.4 mm (95% CI, 19.4-29.4 mm) in the talc group, with a difference of 0.16 mm (95% CI, −6.82 to 7.15; P = .96). There was a statistically significant improvement in dyspnea in the IPC group at 6 months, with a mean difference in VAS score between the IPC group and the talc group of −14.0 mm (95% CI, −25.2 to −2.8 mm; P = .01). Length of initial hospitalization was significantly shorter in the IPC group with a median of 0 days (interquartile range [IQR], 0-1 day) and 4 days (IQR, 2-6 days) for the talc group, with a difference of −3.5 days (95% CI, −4.8 to −1.5 days; P < .001). There was no significant difference in quality of life. Twelve patients (22%) in the talc group required further pleural procedures compared with 3 (6%) in the IPC group (odds ratio [OR], 0.21; 95% CI, 0.04-0.86; P = .03). Twenty-one of the 52 patients in the catheter group experienced adverse events vs 7 of 54 in the talc group (OR, 4.70; 95% CI, 1.75-12.60; P = .002). CONCLUSION Among patients with malignant pleural effusion and no previous pleurodesis, there was no significant difference between IPCs and talc pleurodesis at relieving patient-reported dyspnea. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN87514420.

Case-control study of 24 hour ambulatory blood pressure in patients with obstructive sleep apnoea and normal matched control subjects

BACKGROUND There is considerable debate regarding the relationship between obstructive sleep apnoea (OSA) and hypertension. It is unclear whether OSA is an independent vascular risk factor as studies attempting to assess this association have produced conflicting results because of confounding variables such as upper body obesity, alcohol, and smoking. A case-control study of 24 hour ambulatory blood pressure was undertaken in patients with OSA and matched controls to assess whether OSA is an independent correlate of diurnal hypertension. METHODS Forty five patients with moderate to severe OSA and excessive daytime sleepiness were matched with 45 controls without OSA in a sleep study. Matched variables included age, body mass index (BMI), alcohol, cigarette usage, treated hypertension, and ischaemic heart disease. Upper body obesity was compared by waist:hip and waist:height ratios; 24 hour ambulatory blood pressure recordings were performed (before treatment for OSA) in all subjects. RESULTS Patients with OSA had significantly increased mean (SD) diastolic blood pressure (mm Hg) during both daytime (87.4 (10.2) versus 82.8 (9.1); p=0.03, mean difference 4.6 (95% CI 0.7 to 8.6) and night time (78.6 (9.3) versus 71.4 (8.0); p<0.001, mean difference 7.2 (95% CI 3.7 to 10.6)), and higher systolic blood pressure at night (119.4 (20.7) versus 110.2 (13.9); p=0.01, mean difference 9.2 (95% CI 2.3 to 16.1)). The nocturnal reduction in blood pressure (“dipping”) was smaller in patients with OSA than in control subjects. CONCLUSIONS Compared with closely matched control subjects, patients with OSA have increased ambulatory diastolic blood pressure during both day and night, and increased systolic blood pressure at night. The magnitude of these differences is sufficient to carry an increased risk of cardiovascular morbidity. The slight excess of upper body fat deposition in the controls may make these results conservative.

Management of pleural infection in adults: British Thoracic Society pleural disease guideline 2010

Pleural infection is a frequent clinical problem with an approximate annual incidence of up to 80 000 cases in the UK and USA combined. The associated mortality and morbidity is high; in the UK 20% of patients with empyema die and approximately 20% require surgery to recover within 12 months of their infection.1 2 Prompt evaluation and therapeutic intervention appears to reduce morbidity and mortality as well as healthcare costs.3 This article presents the results of a peer-reviewed systematic literature review combined with expert opinion of the preferred management of pleural infection in adults for clinicians in the UK. The clinical guidelines generated from this process are presented in figure 1. The guidelines are aimed predominantly at physicians involved in adult general and respiratory medicine and specifically do not cover in detail the complex areas of tuberculous empyema, paediatric empyema or the surgical management of post-pneumonectomy space infection. Figure 1 Flow diagram describing the management of pleural infection. This section provides background information for reference, interest and to set the management guidelines in context. ### Historical perspective The Egyptian physician Imhotep initially described pleural infection around 3000 BC, although Hippocrates has been more famously credited with its recognition in 500 BC. Until the 19th century open thoracic drainage was the recommended treatment for this disorder but carried an associated mortality of up to 70%.4 5 This high mortality was probably due to respiratory failure produced by the large open pneumothorax left by drainage.5 This was particularly true of Streptococcus pyogenes infections which produce streptokinase and large alocular effusions free of adhesions.5 Closed tube drainage was first described in 1876 but was not widely adopted until the influenza epidemic of 1917–19. An Empyema Commission subsequently produced recommendations that remain the basis for treatment today. They advocated adequate pus drainage with a closed …

The Relationship Between Chest Tube Size and Clinical Outcome in Pleural Infection

BACKGROUND The optimal choice of chest tube size for the treatment of pleural infection is unknown, with only small cohort studies reported describing the efficacy and adverse events of different tube sizes. METHODS A total of 405 patients with pleural infection were prospectively enrolled into a multicenter study investigating the utility of fibrinolytic therapy. The combined frequency of death and surgery, and secondary outcomes (hospital stay, change in chest radiograph, and lung function at 3 months) were compared in patients receiving chest tubes of differing size (chi(2), t test, and logistic regression analyses as appropriate). Pain was studied in detail in 128 patients. RESULTS There was no significant difference in the frequency with which patients either died or required thoracic surgery in patients receiving chest tubes of varying sizes ( < 10F, number dying or needing surgery 21/58 [36%]; size 10-14F, 75/208 [36%]; size 15-20F, 28/70 [40%]; size > 20F, 30/69 [44%]; chi(2)trend, 1 degrees of freedom [df] = 1.21, P = .27), nor any difference in any secondary outcome. Pain scores were substantially higher in patients receiving (mainly blunt dissection inserted) larger tubes ( < 10F, median pain score 6 [range 4-7]; 10-14F, 5 [4-6]; 15-20F, 6 [5-7]; > 20F, 6 [6-8]; chi(2), 3 df = 10.80, P = .013, Kruskal-Wallis; chi(2)trend, 1 df = 6.3, P = .014). CONCLUSIONS Smaller, guide-wire-inserted chest tubes cause substantially less pain than blunt-dissection-inserted larger tubes, without any impairment in clinical outcome in the treatment of pleural infection. These results suggest that smaller size tubes may be the initial treatment of choice for pleural infection, and randomized studies are now required. TRIAL REGISTRATION MIST1 trial ISRCTN number: 39138989.

Lymphoid interstitial pneumonitis associated with common variable hypogammaglobulinaemia treated with cyclosporin A

Lymphoid interstitial pneumonitis (LIP) is a rare clinicopathological entity that may be associated with common variable immune deficiency (CVID) and may lead to respiratory failure and death. Some patients may respond to prolonged corticosteroid treatment. We hypothesised that, in view of the predominant T cell nature of LIP, cyclosporin A would be a more appropriate choice of immunosuppressive agent and report the first case of its successful use in a woman with LIP associated with CVID.

Blood culture bottle culture of pleural fluid in pleural infection

Background Pleural infection is common, and has a >30% major morbidity and mortality—particularly when infection is caused by Gram-negative, Staphylococcus aureus or mixed aerobic pathogens. Standard pleural fluid culture is negative in ∼40% of cases. Culturing pleural fluid in blood culture bottles may increase microbial yield, and is cheap and easy to perform. Objectives To determine whether inoculating pleural fluid into blood culture bottles increases the culture positivity of pleural infection over standard laboratory culture, and to assess the optimum volume of inoculum to introduce. Methods 62 patients with pleural infection were enrolled. Pairs of aerobic and anaerobic blood culture bottles were inoculated at the bedside with 2, 5 or 10 ml of pleural fluid, and two pleural fluid specimens were sent for standard culture. Pleural fluid from nine control patients was cultured to test for ‘false-positive’ results. Results The addition of blood culture bottle culture to standard culture increased the proportion of patients with identifiable pathogens by 20.8% (20/53 (37.7%) to 31/53 (58.5%) (difference 20.8%, 95% CI difference 8.9% to 20.8%, p<0.001)). The second standard culture did not similarly improve the culture positivity (19/49 (38.8%) to 22/49 (44.9%) (difference 6.1%, 95% CI difference −2.5% to 6.1%, p=0.08)). The culture inoculum volume did not influence bacterial isolation frequency. The control fluids were culture negative. Conclusions Blood culture bottle culture of infected pleural fluid increases microbial yield when used in addition to standard culture. This technique should be part of routine care.

PTPN22 and invasive bacterial disease.

Vang et al.1 recently reported that the protein tyrosine phosphatase PTPN22 Trp620 variant is a gain-of-function mutant, resulting in increased PTPN22 phosphatase activity in T cells. This variant is associated with susceptibility to multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease2, 3, 4, 5, 6. Based on the observation that Trp620 downregulates T cell responses1, we hypothesized that the PTPN22 R620W polymorphism may be associated with susceptibility to invasive bacterial infection.

Mannose-binding lectin genotypes: lack of association with susceptibility to thoracic empyema

BackgroundThe role of the innate immune protein mannose-binding lectin (MBL) in host defence against severe respiratory infection remains controversial. Thoracic empyema is a suppurative lung infection that arises as a major complication of pneumonia and is associated with a significant mortality. Although the pathogenesis of thoracic empyema is poorly understood, genetic susceptibility loci for this condition have recently been identified. The possible role of MBL genotypic deficiency in susceptibility to thoracic empyema has not previously been reported.MethodsTo investigate this further we compared the frequencies of the six functional MBL polymorphisms in 170 European individuals with thoracic empyema and 225 healthy control individuals.ResultsNo overall association was observed between MBL genotypic deficiency and susceptibility to thoracic empyema (2 × 2 Chi square = 0.02, P = 0.87). Furthermore, no association was seen between MBL deficiency and susceptibility to the Gram-positive or pneumococcal empyema subgroups. MBL genotypic deficiency did not associate with progression to death or requirement for surgery.ConclusionsOur results suggest that MBL genotypic deficiency does not associate with susceptibility to thoracic empyema in humans.

A 27-Year-Old Man Presenting With Acute Chest Pain and Dyspnea

(CHEST 2009; 135:1684–1687) A 27-year-old man presented to the emergency department with a 24-h history of dyspnea and right-sided chest pain. The pain was acute in onset, sharp in nature, worse on deep inspiration, did not radiate, and was not reproducible with palpation. There was no associated fever, cough, hemoptysis, or calf pain. The patient denied any history of recent trauma. His medical history included a left-sided acromioclavicular joint dislocation sustained in a road traffic accident that required open reduction 8 months prior to this presentation. The patient was not receiving therapy with any medications and denied smoking or illicit drug use.

British Thoracic Society Guideline for the initial outpatient management of pulmonary embolism (PE)

### Outcomes of outpatient care for low-risk pulmonary embolism (PE) Recommendations ### Inclusion and exclusion criteria for OP management or early discharge Recommendations