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Monitoring treatment response in precapillary pulmonary hypertension using non-invasive haemodynamic measurements

Lee et al should be commended for showing that non-invasive haemodynamic monitoring using inert gas rebreathing (IGR) might be a valuable tool to detect treatment response in patients with precapillary pulmonary hypertension (PH).1 Even under resting conditions, haemodynamic parameters may be more sensitive than the 6-minute walk distance. This is especially interesting as it may facilitate frequent therapy monitoring. Although pulmonary blood flow (PBF) equals cardiac output (CO) in the absence of relevant intrapulmonary shunting, it should be noted that a reliable shunt correction algorithm based on the haemoglobin value has already been implemented in the IGR device.2 Since using solely PBF significantly increased the measurement bias as compared with the non-invasive gold standard of cardiac MRI, shunt correction should always be applied. A fixed haemoglobin concentration of 14.0 g/dl can be used, if the exact value is not known.3 This seems to be...

Are reference equations for spirometry an appropriate criterion for diagnosing disease and predicting prognosis?

In the last few years, there has been considerable debate on the use of threshold criteria for the diagnosis of obstructive lung disease based on FEV1 and FEV1/FVC ratio. It has been argued that a fixed ratio and fixed percentage criterion result in misclassification. The author argues that this critique is based on a false presumption about the validity of reference equations as a criterion for normality. The flaw lies in the methods used to derive reference equations, which involve arbitrary and circular criteria for exclusion of some members of the population, use potentially non-representative reference populations and include predictive variables that are really risk factors for disease or for adverse outcomes of disease. The author argues for a new interpretative approach for the use of lung function data in clinical practice based on prognostic equations analogous to the Framingham cardiovascular risk factor equations. These interpretative equations should be based on data from cohort studies and randomised controlled trials, rather than cross-sectional studies, and if properly formulated, will prove to be valuable aids to clinical decision making.

Differentiation of malignant pleural mesothelioma from other pleural diseases

In this study, pleural effusion samples from 101 patients with suspected or newly diagnosed malignant pleural mesothelioma (MPM) or metastatic adenocarcinoma (ADCA) were collected between 1998 and 2010. Of the 101 patients, 65 were diagnosed with MPM, 25 with ADCA and 15 with benign pleural effusion. Cancer cells isolated from pleural effusion samples were subjected to genome-wide gene expression analysis, done with the help of microarrays and real-time PCR.

The study found 74 genes coding for markers that were overexpressed in MPM and 9 genes that were overexpressed in ADCA. The highest expression in MPM cells was the gene COL3A1, coding for type III collagen. Immunohistochemistry demonstrated 100% staining of MPM biopsy samples with antibodies specific for COL3A1 and no staining in ADCA.

Soluble markers such as CCL2 and galectin-3 were identified as useful markers for diagnosing MPM. CCL2 concentration was significantly higher in patients with MPM than in...

Classifying Lung Function Impairment

Background:

The GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages for COPD use a fixed ratio of the postbronchodilator FEV1/FVC ratio of 0.70 as a threshold to define obstruction. Others advocate using the lower limit of normal (LLN) for the FEV1/FVC ratio, FEV1, and FVC to define abnormality. This study investigated mortality in a representative sample of the US adult population with COPD by comparing abnormality determined using GOLD criteria to that determined using LLN criteria.

Methods:

We used baseline data from the Third National Health and Nutrition Examination Survey and follow-up mortality data. We classified subjects as obstructed, restricted, or normal based on GOLD vs LLN criteria and used Cox proportional hazards models to determine the relation between lung function impairment and mortality, adjusting for covariates.

Results:

The study sample included 13,847 subjects, of whom 3,774 died during the follow-up period. Of subjects classified as obstructed and restricted using GOLD criteria, 20.9% and 18.0%, respectively, were classified as normal using LLN criteria. Compared with people with normal lung function, mortality was increased in the obstructed (hazard ratio, 1.46; 95% CI, 1.21-1.86) and restricted (hazard ratio, 1.94; 95% CI, 1.58-2.39) subjects classified as normal using the LLN.

Conclusions:

In the nationally representative Third National Health and Nutrition Examination Survey data, subjects classified as normal using LLN criteria but obstructed or restricted using GOLD criteria have a higher risk of mortality.

The Impact of Tiotropium on COPD

Background:

Tiotropium has been shown to improve lung function, quality of life, and exacerbations and reduce mortality when compared with placebo in COPD. It remains unclear whether benefits are seen when tiotropium is used in conjunction with inhaled corticosteroids (ICSs) plus long-acting β-agonists (LABAs).

Methods:

We performed a retrospective cohort study using a National Health Service database of patients with COPD in Tayside, Scotland, between 2001 and 2010 that is linked with databases regarding hospital admissions, pharmacy prescriptions, and death registries. The impact of the addition of tiotropium (Tio) to ICS + LABA therapy on all-cause mortality, hospital admissions for respiratory disease, and emergency oral corticosteroid bursts was evaluated. Adjusted hazard ratios (HRs) were calculated by Cox regression after inclusion of the following covariates: cardiovascular and respiratory disease, diabetes, smoking, age, sex, and deprivation index.

Results:

A total of 1,857 patients were given ICS + LABA + Tio, and 996 were given ICS + LABA. Mean follow-up was 4.65 years. The adjusted HR for all-cause mortality for ICS + LABA + Tio vs ICS + LABA was 0.65 (95% CI, 0.57-0.75; P < .001). Adjusted HRs for hospital admissions and oral corticosteroid bursts were 0.85 (95% CI, 0.73-0.99; P = .04) and 0.71 (95% CI, 0.63-0.80; P < .001), respectively.

Conclusions:

The study suggests that the addition of tiotropium to ICSs and LABA therapy may confer benefits in reducing all-cause mortality, hospital admissions, and oral corticosteroid bursts in patients with COPD. Triple therapy is widely used in the real-life management of COPD, with only limited scientific support. The study supports the use of triple therapy in COPD and provides a platform for randomized controlled trials specifically addressing this topic.

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