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Imaging in pulmonary hypertension, part 2: large vessel diseases.

Pulmonary hypertension is defined by physiological parameters but there are numerous causes that differ in their pathogenesis, management and prognosis. Causes include chronic cardiac or pulmonary diseases and diffuse small vessel disease but also a range of large vessel obstructive diseases.

The physiological manifestation of all these diseases is increased pulmonary vascular resistance and pulmonary arterial hypertension, and while clinical features may provide a clue to diagnosis, imaging plays a fundamental role in establishing a precise diagnosis and therefore guiding therapy. Chronic thromboembolic pulmonary hypertension (CTEPH) is the most common large vessel cause of pulmonary hypertension. It is increasingly recognised as a major cause of morbidity and mortality which is underdiagnosed and often diagnosed late. The importance of CTEPH is that for patients in whom the distribution of disease lies predominantly in the proximal vasculature there is potential for symptomatic and physiological cure by surgical pulmonary endarterectomy.

More distal disease may be suitable for medical management. Increased awareness on behalf of both clinicians and imagers is therefore paramount. However, there are other rare causes or large vessel obstruction/stenosis such as large vessel vasculitis, pulmonary artery tumour, fibrosing mediastinitis, congenital stenosis or extrinsic compression of the pulmonary arteries/veins. Atypical imaging appearance such as unilateral central pulmonary artery obstruction should lead to consideration of a diagnosis other than CTEPH.

Complexity of Medication Use in Newly Diagnosed Chronic Obstructive Pulmonary Disease Patients.

To better understand how medications have been used and the complexity of regimens used to treat patients, we characterized patterns of medication use and the degree to which patients used different classes of medications in combination and over time in a cohort of newly diagnosed chronic obstructive pulmonary disease (COPD) patients.

OBJECTIVE: The objectives of this study were to characterize patterns of medication use, including the degree to which patients used different classes of medications in combination and over time within a cohort of newly diagnosed COPD patients and to identify the proportion of patients who had gaps in filling their prescriptions.

METHODS: We identified a cohort of patients from the Veterans Affairs health care system with newly diagnosed COPD between 1999 and 2003. Using prescription fill information, we quantified the prevalence and incidence of exposure to short-acting β-agonists (SABAs), long-acting β-agonists (LABAs), short-acting anticholinergics (eg, ipratropium [IPRA]), and inhaled corticosteroids (ICSs) over 1 year. We additionally characterized the sequencing of medication addition and discontinuation and gaps between prescription fills. The prevalence of multiple respiratory medication use was summarized at 90, 180, and 365 days of follow-up.

RESULTS: Of 133,737 patients with newly diagnosed COPD, the majority (80.0%) used a SABA, followed by 40.0% using IPRA, 33.2% using an ICS and 16.0% using a LABA during the 1-year follow-up. Medication changes were frequent, with 57.7% of patients having a medication addition and 48.6% discontinuing medication. The sequence of medication changes varied greatly across patients. Multiple respiratory medication use was common, with 29% of patients dispensed 3 to 4 medication classes in 1 year.

CONCLUSIONS: Many COPD patients who are started on medication management undergo changes in prescribed pharmacotherapy and are taking multiple medications. Despite clinical practice guidelines, there is an ad hoc nature of COPD medication management, and such heterogeneity challenges the ability to estimate relationships between drug exposure and outcomes using real-world data.

Tests of the Responsiveness of the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test TM (CAT) Following Acute Exacerbation and Pulmonary Rehabilitation.

The chronic obstructive pulmonary disease (COPD) Assessment Test™ (CAT) is an eight-item questionnaire suitable for routine clinical use that shows reliability and validity in stable and exacerbating COPD.

METHODS:Study 1 assessed CAT responsiveness to changes in health status in 67 patients during an exacerbation, (Days 1-14). Study 2 assessed CAT responsiveness in 64 patients undergoing pulmonary rehabilitation, (Days 1-42). Correlations between CAT and other outcome measures were examined.

RESULTS:In Study 1, mean 14-day improvement in CAT score was -1.4 units ± 5.3 (p = 0.03). In patients judged to be responders (clinician-defined) change in score was -2.6 ± 4.4; in non-responders it was -0.2 ± 5.9. In Study 2, the mean improvement in CAT score was -2.2 ± 5.3 (p = 0.002); the effect size for the change was -0.33. Effect size for changes in the Chronic Respiratory Questionnaire - Self Administered Standardized form (CRQ-SAS) domain scores ranged from -0.02 to 0.34. Change in 6-minute walk distance was 41 ± 55 m. CAT and CRQ-SAS domain scores correlated at baseline (r = -0.54 to -0.69, p < 0.0001) and in terms of change following pulmonary rehabilitation (r = -0.39 to -0.63, p < 0.01). Correlations were less strong between change in the CAT and SGRQ in Study 1 (r<0.24), and for 6-minute walk distance (r<0.11) in Study 2.

CONCLUSIONS:These studies indicate that the CAT is sensitive to changes in health status following exacerbations and is as responsive to pulmonary rehabilitation as more complex COPD health status measures.

Prognostic value of the objective measurement of daily physical activity in COPD patients.

Subjective measurement of physical activity using questionnaires has prognostic value in COPD. However, their lack of accuracy and large individual variability limit their use for evaluation on an individual basis. We evaluate the capacity of the objective measurement of daily physical activity in COPD patients using accelerometers to estimate their prognostic value.

METHODS : In 173 consecutive subjects with moderate-very severe COPD, daily physical activity was measured using a triaxial accelerometer providing a mean of 1-minute movement epochs as vector magnitude units (VMU). Patients were evaluated by lung function testing and six-minute walk, incremental exercise and constant-work rate tests. Patients were followed during 5-8 years and the end points were all-cause mortality, hospitalization for COPD exacerbation and annual declining FEV(1).

RESULTS : After adjusting for relevant confounders, a high VMU decreases the mortality risk (adjusted hazard ratio [HR]: 0.986 [95%CI 0.981-0.992]) and in a multivariate model, comorbidity, endurance time and VMU were retained as independent predictors of mortality. The time until first admission due to COPD exacerbation was shorter for the patients with lower levels of VMU (adjusted HR: 0.989 [95%CI 0.983-0.995]). Moreover, patients with higher VMU had a lower hospitalization risk than those with a low VMU (adjusted incidence rate ratio: 0.099 [95%CI 0.033-0.293). In contrast, VMU was not identified as an independent predictor of the annual FEV(1) decline.

CONCLUSION : The objective measurement of the daily physical activity in COPD patients using an accelerometer constitutes an independent prognostic factor for mortality and hospitalization due to severe exacerbation.

Utility of the COPD Assessment Test&trade; (CAT) to Evaluate Severity of COPD Exacerbations.

The COPD Assessment Test™ (CAT) is an 8-item questionnaire designed to assess and quantify the impact of COPD symptoms on health status. COPD exacerbations impair quality of life and are characterized by worsening respiratory symptoms from the stable state. We hypothesized that CAT scores at exacerbation relate to exacerbation severity as measured by exacerbation duration, lung function impairment and systemic inflammation.

OBJECTIVES: To evaluate the utility of the CAT to assess exacerbation severity.

METHODS: 161 patients enrolled in the London COPD cohort completed the CAT at baseline (stable state), exacerbation and during recovery between April 2010 and June 2011.

MEASUREMENTS AND MAIN RESULTS: Frequent exacerbators had significantly higher baseline CAT scores than infrequent exacerbators (19.5±6.6 vs. 16.8±8.0, p=0.025). In 152 exacerbations, CAT scores rose from an average baseline value of 19.4±6.8 to 24.1±7.3 (p<0.001) at exacerbation. Change in CAT score from baseline to exacerbation onset was significantly but weakly related to change in CRP (rho=0.26; p=0.008) but not to change in fibrinogen (rho=0.09, p=0.351) from baseline to exacerbation. At exacerbation, rises in CAT score were significantly associated with falls in FEV1 (rho=-0.20, p=0.032). Median recovery time as judged by symptom diary cards was significantly related to the time taken for the CAT score to return to baseline (rho=0.42; p=0.012).

CONCLUSIONS: The CAT provides a reliable score of exacerbation severity. Baseline CAT scores are elevated in frequent exacerbators. CAT scores increase at exacerbation and reflect severity as determined by lung function and exacerbation duration.

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