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Frequency and risk factors of COPD exacerbations and hospitalizations: a nationwide study in Greece (Greek Obstructive Lung Disease Epidemiology and health ecoNomics: GOLDEN study).

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BACKGROUND: COPD exacerbations and hospitalizations have been associated with poor prognosis for the COPD patient.
OBJECTIVE: To evaluate the frequency and risk factors of COPD exacerbations, hospitalizations, and admissions to intensive care units (ICUs) in Greece by a nationwide cross-sectional study.

MATERIALS AND METHODS: A nationwide observational, multicenter, cross-sectional study was conducted in the clinical practice setting of respiratory medicine physicians over a 6 month-period (October 2010 to March 2011). A total of 6,125 COPD patients were recruited by 199 respiratory physicians.

RESULTS: Participants had a median age of 68.0 years, 71.3% were males, and 71.8% suffered from comorbidities. The median disease duration was 10.0 years. Of the patients, 45.3% were classified as having GOLD (Global initiative for chronic Obstructive Lung Disease) stage III or IV COPD. Patients with four or more comorbidities had 78.5% and threefold-higher than expected number of exacerbations and hospitalizations, respectively, as well as fivefold-higher risk of admission to the ICU compared to those with no comorbidities. Obese patients had 6.2% fewer expected exacerbations compared to those with a normal body mass index. Patients with GOLD stage IV had 74.5% and fivefold-higher expected number of exacerbations and hospitalizations, respectively, and nearly threefold-higher risk of admission to the ICU compared to stage I patients. An additional risk factor for exacerbations and hospitalizations was low compliance with treatment: 45% of patients reported forgetting to take their medication, and 81% reported a preference for a treatment with a lower dosing frequency.

CONCLUSION: Comorbidities, disease severity, and compliance with treatment were identified as the most notable risk factors for exacerbations, hospitalizations, and ICU admissions. The results point to the need for a multifactorial approach for the COPD patient and for the development of strategies that can increase patient compliance with treatment.

Understanding the pathophysiology of the asthma-chronic obstructive pulmonary disease overlap syndrome.

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PURPOSE OF REVIEW: The review will provide an update on the pathophysiology and studies of inflammation associated with the asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and the mechanism(s) responsible for persistent expiratory airflow limitation in never-smoked asthma patients who develop loss of lung elastic recoil consistent with an asthma-COPD clinical phenotype (ACOS in nonsmokers).

RECENT FINDINGS: Patients with a clinical diagnosis of ACOS have more frequent respiratory exacerbations and hospitalizations than COPD patients without ACOS. ACOS patients should be treated with inhaled corticosteroids, short and long-acting β2-agonist, and long-acting muscarinic receptor antagonist. Biomarker work suggests that a molecular phenotype of ACOS (e.g., elevated markers of eosinophilic or type 2 inflammation) incompletely corresponds to clinical phenotypes. Recently, we reported sentinel observation of unsuspected mild diffuse centrilobular emphysema in never-smoked asthma patients at autopsy, despite mild changes in lung computed tomography and normal diffusing capacity.

SUMMARY: Recent studies have shown that subgroups of COPD and asthma patients may have overlapping immune responses. Never-smoked asthma patients may have persistent expiratory airflow limitation because of loss of lung elastic recoil. This may be because of unsuspected centrilobular emphysema detected at autopsy, and not easily diagnosed on lung computed tomography and diffusing capacity.

Disease phenotyping in chronic obstructive pulmonary disease: the neutrophilic endotype.

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PURPOSE OF REVIEW: Despite decades of scientific attention, chronic obstructive pulmonary disease (COPD) remains a major cause of both morbidity and mortality worldwide with strikingly few effective drug classes available. This may be in part because COPD is actually a syndrome composed of distinct diseases with varying pathophysiology (endotypes), and therapies have not been designed to target the causal pathological processes specific to an endotype.

RECENT FINDINGS: Recent work has begun to clarify the nature of these endotypes and characterize them. One promising field focuses on the central role of the neutrophil and the tripeptide matrikine proline-glycine-proline (PGP) in a subset of COPD patients. Two drugs with mechanisms of action novel to the COPD therapeutic arena (azithromycin and roflumilast) have been shown to reduce acute exacerbations of COPD. Intriguingly, recent evidence has linked both of these agents to modulation of the PGP/neutrophil pathway in concert with this exacerbation reduction, suggesting that a neutrophilic endotype is present and amenable to pharmacological targeting.

SUMMARY: Further work characterizing COPD endotypes, including this neutrophilic endotype, will be important as we strive to understand the mechanistic roots of this disease in the hope of creating more effective therapies.

Long-term noninvasive ventilation in patients with chronic hypercapnic respiratory failure: assisting the diaphragm, but threatening the heart?

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PURPOSE OF REVIEW: To summarize and discuss the available studies on the effects of long-term noninvasive ventilation (NIV) on cardiac function in patients with chronic hypercapnic respiratory failure.

RECENT FINDINGS: A total of nine studies investigated the acute and long-term effects of NIV on cardiac performance in patients with chronic hypercapnic respiratory failure.

SUMMARY: Both the application of expiratory airway pressure and (higher) inspiratory pressures may acutely decrease cardiac output during the initiation of NIV. However, the meaning of this effect in the long term is not clear. Apparently, natriuretic peptides decrease after a certain period of NIV use and heart rate variability seems to improve. Probably, a decreased cardiac output might not be disadvantageous and reflects a decreased work of breathing. Furthermore, the hemodynamic effects of long-term NIV are dependent on the underlying cardiac comorbidities. This is important in patients with chronic obstructive pulmonary disease, where cardiac comorbidities are frequent.Considering the available physiological data, future studies should focus on the impact of long-term NIV on heart performance and clinical outcomes. Second, further studies are needed investigating the cardiac long-term effects of different NIV modes, pressures (low and high) and breathing frequencies, especially when underlying cardiac comorbidity is present.

Can transcutaneous carbon dioxide pressure be a surrogate of blood gas samples for spontaneously breathing emergency patients? The ERNESTO experience.

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It is known that the arterial carbon dioxide pressure (PaCO2) is useful for emergency physicians to assess the severity of dyspnoeic spontaneously breathing patients. Transcutaneous carbon dioxide pressure (PtcCO2) measurements could be a non-invasive alternative to PaCO2 measurements obtained by blood gas samples, as suggested in previous studies. This study evaluates the reliability of a new device in the emergency department (ED).

METHODS: We prospectively included patients presenting to the ED with respiratory distress who were breathing spontaneously or under non-invasive ventilation. We simultaneously performed arterial blood gas measurements and measurement of PtcCO2 using a sensor placed either on the forearm or the side of the chest and connected to the TCM4 CombiM device. The agreement between PaCO2 and PtcCO2 was assessed using the Bland-Altman method.

RESULTS: Sixty-seven spontaneously breathing patients were prospectively included (mean age 70 years, 52% men) and 64 first measurements of PtcCO2 (out of 67) were analysed out of the 97 performed. Nineteen patients (28%) had pneumonia, 19 (28%) had acute heart failure and 19 (28%) had an exacerbation of chronic obstructive pulmonary disease. Mean PaCO2 was 49 mm Hg (range 22-103). The mean difference between PaCO2 and PtcCO2 was 9 mm Hg (range -47 to +54) with 95% limits of agreement of -21.8 mm Hg and 39.7 mm Hg. Only 36.3% of the measurement differences were within 5 mm Hg.

CONCLUSIONS: Our results show that PtcCO2 measured by the TCM4 device could not replace PaCO2 obtained by arterial blood gas analysis.

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